Pyrroles having hypolipidemic hypocholesteremic activities, process for their preparation and pharmaceutical compositions containing them and their use in medicine

ABSTRACT

The present invention relates to novel substituted pyrrole compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. This invention particularly relates to novel substituted pyrrole compounds of the general formula (I), their analogs, their derivatives, their polymorphs, their tautomeric forms, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and their pharmaceutical compositions containing them. The invention also relates to the process for preparing such compounds, a composition containing such a compound and the use of such a compound and composition in medicine. The compounds lower triglyceride levels in blood and may be useful in the treatment of obesity, hyperlipidaemia, hypercholesteremia, syndrome X and diabetes.

FIELD OF INVENTION

The present invention relates to novel hypolipidaemic and hypocholesterolemic compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. More particularly, the present invention relate to novel β-aryl-α-substituted propanoic acids of the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, pharmaceutical compositions containing them, use of these compounds in medicine and the intermediates involved in their preparation.

The present invention also relates to a process for the preparation of the above said novel compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, and pharmaceutical compositions containing them.

The compounds of the general formula (I) lower or modulate triglyceride levels and/or cholesterol levels and/or low-density lipoproteins (LDL) and raise HDL plasma levels and hence are useful in combating different medical conditions, where such lowering (and raising) is beneficial. Thus, it could be used in the treatment and/or prophylaxis of obesity, hyperlipidaemia, hypercholesteremia, hypertension, atherosclerotic disease events, vascular restenosis, diabetes and many other related conditions. The compounds of general formula (I) are useful to prevent or reduce the risk of developing atherosclerosis, which leads to diseases and conditions such as arteriosclerotic cardiovascular diseases, stroke, coronary heart diseases, cerebrovascular diseases, peripheral vessel diseases and related disorders.

These compounds of general formula (I) are useful for the treatment and/or prophylaxis of metabolic disorders loosely defined as Syndrome X. The characteristic features of Syndrome X include initial insulin resistance followed by hyperinsulinemia, dyslipidemia and impaired glucose tolerance. The glucose intolerance can lead to non-insulin dependent diabetes mellitus (NIDDM, Type 2 diabetes), which is characterized by hyperglycemia, which if not controlled may lead to diabetic complications or metabolic disorders caused by insulin resistance. Diabetes is no longer considered to be associated only with glucose metabolism, but it affects anatomical and physiological parameters, the intensity of which vary depending upon stages/duration and severity of the diabetic state. The compounds of this invention are also useful in prevention, halting or slowing progression or reducing the risk of the above mentioned disorders along with the resulting secondary diseases such as cardiovascular diseases, like arteriosclerosis, atherosclerosis; diabetic retinopathy, diabetic neuropathy and renal disease including diabetic nephropathy, glomerulonephritis, glomerular sclerosis, nephrotic syndrome, hypertensive nephrosclerosis and end stage renal diseases, like microalbuminuria and albuminuria, which may be result of hyperglycemia or hyperinsulinemia.

The compounds of the present invention can be useful as aldose reductase inhibitors; for improving cognitive functions in dementia, and in the treatment and/or prophylaxis of disorders such as psoriasis, polycystic ovarian syndrome (PCOS), cancer, osteoporosis, leptin resistance, inflammation and inflammatory bowel diseases, xanthoma, pancreatitis, myotonic dystrophy, endothelial cell dysfunction and hyperlipidemia.

The compounds of the present invention are useful in the treatment of the diseases mentioned herein, alone or in combination one or more hypoglycemic, antihyperglycemic, hypolipidaemic, hypolipoproteinemic agents, antioxidants, antihypertensives, such as HMG CoA reductase inhibitor, fibrate, statins, glitazones, sulfonyl ureas, insulin, α-glycosidase inhibitors, nicotinic acid, cholestyramine, cholestipol or probucol, and the like.

BACKGROUND OF THE INVENTION

Hyperlipidaemia has been recognized as the major risk factor in causing cardiovascular diseases due to atherosclerosis. Atherosclerosis and other such peripheral vascular diseases affect the quality of life of a large population in the world. The therapy aims to lower the elevated plasma LDL cholesterol, low-density lipoprotein and plasma triglycerides in order to prevent or reduce the risk of occurrence of cardiovascular diseases. The detailed etiology of atherosclerosis and coronary artery diseases is discussed by Ross and Glomset [New Engl. J. Med., 295, 369-377 (1976)]. Plasma cholesterol is generally found esterified with various serum lipoproteins and numerous studies have suggested an inverse relationship between serum HDL-cholesterol level and risk for occurrence of cardiovascular disease. Many studies have suggested an increased risk of coronary artery diseases (CAD) due to elevated LDL and VLDL-cholesterol levels [Stampfer et al., N. Engl. J. Med., 325, 373-381 (1991)]. The other studies illustrate protective effects of HDL against progression of atherosclerosis. Thus, HDL has become a crucial factor in treating diseases with increased levels of cholesterol [Miller et. al., Br. Med. J. 282, 1741-1744 (1981); Picardo et al., Arteriosclerosis, 6, 434-441 (1986); Macikinnon et al., J. Biol. Chem. 261, 2548-2552 (1986)].

Diabetes is associated with a number of complications and also affect a large population. This disease is usually associated with other diseases such as obesity, hyperlipidemia, hypertension and angina. It is well established that improper treatment can aggravate impaired glucose tolerance and insulin resistance, thereby leading to frank diabetes. Further, patients with insulin resistance and type 2 diabetes often have raised triglycerides and low HDL-cholesterol concentrations and therefore, have greater risk of cardiovascular diseases. The present therapy for these diseases includes sulfonylureas and biguanides along with insulin. This type of drug therapy may lead to mild to severe hypoglycemia, which may lead to coma or in some cases may lead to death, as a result of unsatisfactory glycaemic control by these drugs. Recent addition of drugs in the treatment of diabetes are the thiazolidinediones, drugs having insulin-sensitizing action. Thiazolidinediones are prescribed alone or in combination with other anti-diabetic agents like troglitazone, rosiglitazone and pioglitazone. These are useful in treating diabetes, lipid metabolism but are suspected to have tumor-inducing potential and cause hepatic dysfunction, which may lead to liver failure. Further, serious undesirable side-effects have occurred in animal and/or human studies which include cardiac hypertrophy, hema dilution and liver toxicity in a few glitazones progressing to advanced human trials. The drawback is considered to be idiosyncratic. Presently, there is a need for a safe and an effective drug, to treat insulin resistance, diabetes and hyperlipidemia. [Exp. Clin. Endocrinol. Diabetes: 109(4), S548-9 (2001)]

Obesity is another major health problem being associated with increased morbidity and mortality. It is a metabolic disorder, in which excess of fat is accumulated in the body. Although, its etiology is unclear, the general feature includes excess of calorie intake than it is consumed. Various therapies such as dieting, exercise, appetite suppression, inhibition of fat absorption etc. have been used to combat obesity. However, more efficient therapies to treat this abnormality is essential as obesity is closely related to several diseases such as coronary heart disease, stroke, diabetes, gout, osteoarthritis, hyperlipidaemia and reduced fertility. It also leads to social and psychological problems. [Nature Reviews: Drug Discovery: 1(4), 276-86 (2002)]

Peroxisome Proliferator Activated Receptor (PPAR) is a member of the steroid/retinoid/thyroid hormone receptor family. PPAR∝, PPARγ and PPARδ have been identified as subtypes of PPARs. Extensive reviews regarding PPAR, their role in different diseased conditions are widely published [Endocrine Reviews, 20(5), 649-688 (1999); J. Medicinal Chemistry, 43(4), 58-550 (2000); Cell, 55, 932-943 (1999); Nature, 405, 421-424 (2000); Trends in Pharmacological Sci., 469-473 (2000)]. PPARγ activation has been found to play a central role in initiating and regulating adipocyte differentiation [Endocrinology 135, 798-800, (1994)] and energy homeostasis, [Cell, 83, 803-812 (1995); Cell, 99, 239-242 (1999)]. PPARγ agonists would stimulate the terminal differentiation of adipocyte precursors and cause morphological and molecular changes characteristic of a more differentiated, less malignant state. During adipocyte differentiation, several highly specialized proteins are induced, which are being involved in lipid storage and metabolism. It is accepted that PPARγ activation leads to expression of CAP gene [Cell biology, 95, 14751-14756, (1998)], however, the exact link from PPARγ activation to changes in glucose metabolism and decrease in insulin resistance in muscle has not been clear. PPARα is involved in stimulating β-oxidation of fatty acids [Trends Endocrine. Metabolism, 4, 291-296 (1993)] resulting in plasma circulating free fatty acid reduction [Current Biol., 5, 618-621 (1995)]. Recently, role of PPARγ activation in the terminal differentiation of adipocyte precursors has been implicated in the treatment of cancer. [Cell, 79, 1147-1156 (1994); Cell, 377-389 (1996); Molecular Cell, 465-470 (1998); Carcinogenesis, 1949-1953 (1998); Proc. Natl. Acad. Sci., 94, 237-241 (1997); Cancer Research, 58, 3344-3352 (1998)]. Since PPARγ is expressed in certain cells consistently, PPARγ agonists would lead to nontoxic chemotherapy. There is growing evidence that PPAR agonists may also influence the cardiovascular system through PPAR receptors as well as directly by modulating vessel wall function [Med. Res. Rev., 20 (5), 350-366 (2000)].

PPAR α agonists have been found useful in the treatment of obesity (WO 97/36579). Dual PPAR α, and γ agonists have been suggested to be useful for Syndrome X (WO 97/25042). PPAR δ agonists and HMG-CoA reductase inhibitors have exhibited synergism and indicated the usefulness of the combination in the treatment of atherosclerosis and xanthoma (EP 0753 298).

Leptin is a protein when bound to leptin receptors is involved hi sending satiety signal to the hypothalamus. Leptin resistance would therefore lead to excess food in-take, reduced energy expenditure, obesity, impaired glucose tolerance and diabetes [Science, 269, 543-46 (1995)]. It has been reported that insulin sensitizers lower plasma leptin concentration [Proc. Natl. Acad. Sci. 93, 5793-5796 (1996): WO 98/02159)].

A number of compounds belonging to β-aryl-α-hydroxypropanoic acids and their derivatives have been reported to be useful in the treatment of hyperlipidemia, hypercholesterolemia and hyperglycemia [U.S. Pat. No. 5,306,726, U.S. Pat. No. 5,985,884, U.S. Pat. No. 6,054,453, U.S. Pat. No. 6,130,214, EP 90 3343, PCT publications Nos. WO 91/19702, WO 94/01420, WO 94/13650, WO 95/03038, WO 95/17394, WO 96/04260, WO 96/04261, WO 96/33998, WO 97/25042, WO 97/36579, WO 98/28534, WO 99/08501, WO 99/16758, WO 99/19313, WO99/20614, WO 00/23417, WO 00/23445, WO 00/23451, WO 01/53257].

SUMMARY OF INVENTION

The objective of this invention is to develop novel compounds represented by the general formula (I) used as hypocholesterolemic, hypolipidaemic, hypolipoproteinemic, anti-obesity and antihyperglycemic agents which may have additional body weight lowering effect and beneficial effect in the treatment and/or prophylaxis of diseases caused by hyperlipidaemia, diseases classified under syndrome X and atherosclerosis.

The main objective of the present invention is to provide novel β-aryl-α-substituted propanoic acids represented by the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, and pharmaceutical compositions containing them or their mixtures thereof.

Another objective of the present invention is to provide novel β-aryl-α-substituted propanoic acids represented by the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, and pharmaceutical compositions containing them or their mixtures thereof having enhanced activities, without toxic effects or with reduced toxic effect.

Yet another objective of this invention is to provide a process for the preparation of novel β-aryl-α-substituted propanoic acids represented by the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates.

Still another objective of the present invention is to provide pharmaceutical compositions containing compounds of the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates or their mixtures in combination with suitable carriers, solvents, diluents and other media normally employed in preparing such compositions.

A further objective of the present invention is to provide process for preparation of intermediates involved in the process.

DETAILED DESCRIPTION OF THE INVENTION

Accordingly, the present invention relates to compounds of the general formula (I),

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, wherein R¹ and R³ represent hydrogen, and R¹, R⁴ may be same or different, and independently represent hydrogen, haloalkyl, perhaloalkyl, nitro, cyano, formyl, or substituted or unsubstituted groups selected from linear or branched (C₁-C₆)alkyl, linear or branched (C₂-C₆)alkenyl, linear or branched (C₂-C₆)alkynyl, (C₃-C₇)cycloalkyl, (C₃-C₇)cycloalkenyl, aryl, aralkyl, heterocyclyl, heteroaryl, heterocyclyl(C₁-C₆)alkyl, heteroar(C₁-C₆)alkyl, acyl, acyloxy, carboxylic acid and its derivatives such as esters and amides, hydroxyalkyl, aminoalkyl, mono-substituted or di-substituted aminoalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, (C₁-C₆)alkylthio, thio(C₁-C₆)alkyl, arylthio, derivatives of sulfenyl and sulfonyl groups, sulfonic acid and its derivatives; n represents an integer 2, W represents O, S or NR⁹, where R⁹ represents hydrogen, (C₁-C₆)alkyl or aryl groups; Ar represents a substituted or unsubstituted divalent single or fused aromatic, heteroaromatic group; R⁵ and R⁶ represent both hydrogen or together represent a bond; X represent O or S; R⁷ represents hydrogen, perfluoro(C₁-C₁₂)alkyl, substituted or unsubstituted groups selected from linear or branched (C₁-C₁₂)alkyl, cyclo(C₃-C₆)alkyl, aryl, ar(C₁-C₁₂)alkyl, heteroaryl, heteroar(C₁-C₁₂)alkyl, heterocyclyl, alkoxyalkyl, aryloxyalkyl, alkoxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl or acyl groups; Y represents O or S; Z represents O, S or NR¹⁰ where R¹⁰ represents hydrogen or substituted or unsubstituted groups selected from (C₁-C₆)alkyl, aryl, ar(C₁-C₆)alkyl, hydroxy(C₁-C₆)alkyl, amino(C₁-C₆)alkyl, heteroaryl or heteroar(C₁-C₆)alkyl groups; R⁸ represents hydrogen, substituted or unsubstituted groups selected from linear or branched (C₁-C₆)alkyl, aryl, ar(C₁-C₆)alkyl, heteroaryl, heteroar(C₁-C₆)alkyl, heterocylyl, heterocyclylalkyl, hydroxyalkyl, alkoxyalkyl or alkylaminoalkyl groups; R¹⁰ and R⁸ together may form 5 or 6 membered substituted or unsubstituted heterocyclic ring structure containing one or more heteroatoms selected from O, N or S.

The various groups, radicals and substituents used anywhere in the specification are described in the following paragraphs, unless it is specifically described otherwise:

The term “alkyl” used herein, either alone or in combination with other radicals, denotes a linear or branched radical containing one to twelve carbons, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, amyl, t-amyl, n-pentyl, n-hexyl, iso-hexyl, heptyl, octyl and the like.

The term “alkenyl” used herein, either alone or in combination with other radicals, denotes a linear or branched radical containing one to twelve carbons such as vinyl, allyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2 heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl and the like. The term “alkenyl” includes dienes and trienes of straight and branched chains.

The term “alkynyl” used herein, either alone or in combination with other radicals, denotes a linear or branched radical containing one to twelve carbons, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, and the like. The term “alkynyl” includes di- and tri-ynes.

The term “cyclo(C₃-C₇)alkyl” used herein, either alone or in combination with other radicals, denotes a radical containing three to seven carbons, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and the like.

The term “cyclo(C₃-C₇)alkenyl” used herein, either alone or in combination with other radicals, denotes a radical containing three to seven carbons, such as cyclopropenyl, 1-cyclobutenyl, 2-cyclobutenyl, 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 1-cycloheptenyl, cycloheptadienyl, cycloheptatrienyl, and the like.

The term “alkoxy” used herein, either alone or in combination with other radicals, denotes a radical alkyl, as defined above, attached directly to an oxygen atom, such as methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, t-butoxy, iso-butoxy, pentyloxy, hexyloxy, and the like.

The term “alkenoxy” used herein, either alone or in combination with other radicals, denotes an alkenyl radical, as defined above, attached to an oxygen atom, such as vinyloxy, allyloxy, butenoxy, pentenoxy, hexenoxy, and the like.

The term “cyclo(C₃-C₇)alkoxy” used herein, either alone or in combination with other radicals, denotes a radical containing three to seven carbon atoms, such as cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy and the like.

The term “halo” or “halogen” used herein, either alone or in combination with other radicals, such as “haloalkyl”, “perhaloalkyl” etc refers to a fluoro, chloro, bromo or iodo group. The term “haloalkyl” denotes a radical alkyl, as defined above, substituted with one or more halogens such as perhaloalkyl, more preferably, perfluoro(C₁-C₆)alkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, mono or polyhalo substituted methyl, ethyl, propyl, butyl, pentyl or hexyl groups. The term “haloalkoxy” denotes a haloalkyl, as defined above, directly attached to an oxygen atom, such as fluoromethoxy, chloromethoxy, fluoroethoxy chloroethoxy groups, and the like. The term “perhaloalkoxy” denotes a perhaloalkyl radical, as defined above, directly attached to an oxygen atom, trifluoromethoxy, trifluoroethoxy, and the like.

The term “aryl” or “aromatic” used herein, either alone or in combination with other radicals, refers to an optionally substituted aromatic system containing one, two or three rings wherein such rings may be attached together in a pendant manner or may be fused, such as phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl, and the like. The term “aralkyl” denotes an alkyl group, as defined above, attached to an aryl, such as benzyl, phenethyl, naphthylmethyl, and the like. The term “aryloxy” denotes an aryl radical, as defined above, attached to an alkoxy group, such as phenoxy, naphthyloxy and the like, which may be substituted. The term “aralkoxy” denotes an arylalkyl moiety, as defined above, such as benzyloxy, phenethyloxy, naphthylmethyloxy, phenylpropyloxy, and the like, which may be substituted. The term “heterocyclyl” or “heterocyclic” used herein, either alone or in combination with other radicals is intended to include a saturated, partially saturated and unsaturated ring-shaped radicals, the heteroatoms selected from nitrogen, sulfur and oxygen. Examples of saturated heterocyclic radicals include aziridinyl, azetidinyl, benzothiazolyl, pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, 2-oxopiperidinyl, 4-oxopiperidinyl, 2-oxopiperazinyl, 3-oxopiperazinyl, morpholinyl, thiomorpholinyl, 2-oxomorpholinyl, azepinyl, diazepinyl, oxapinyl, thiazepinyl, oxazolidinyl, thiazolidinyl, and the like; examples of partially saturated heterocyclic radicals include dihydrothiophene, dihydropyran, dihydrofuran, dihydrothiazole, and the like.

The term “heteroaryl” or “heteroaromatic” used herein, either alone or in combination with other radicals, represents an optionally substituted unsaturated 5 to 6 membered heterocyclic radicals containing one or more hetero atoms selected from O, N or S, attached to an aryl group, such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, oxadiazolyl, tetrazolyl, benzopyranyl, benzofuranyl, benzothienyl, indolinyl, indolyl, quinolinyl, pyrimidinyl, pyrazolyl, quinazolinyl, pyrimidonyl, benzoxazinyl, benzoxazinonyl, benzothiazinyl, benzothiazinonyl, benzoxazolyl, benzothizaolyl, benzimidazolyl, and the like.

The term “heterocyclyl(C₁-C₁₂)alkyl” used herein, either alone or in combination with other radicals, represents a heterocyclyl group, as defined above, substituted with an alkyl group of one to twelve carbons, such as pyrrolidinealkyl, piperidinealkyl, morpholinealkyl, thiomorpholinealkyl, oxazolinealkyl, and the like, which may be substituted. The term “heteroaralkyl” used herein, either alone or in combination with other radicals, denotes a heteroaryl group, as defined above, attached to a straight or branched saturated carbon chain containing 1 to 6 carbons, such as (2-furyl)methyl, (3-furyl)methyl, (2-thienyl)methyl, (3-thienyl)methyl, (2-pyridyl)methyl, 1-methyl-1-(2-pyrimidyl)ethyl and the like. The terms “heteroaryloxy”, “heteroaralkoxy”, “heterocycloxy”, “heterocylylalkoxy” denotes heteroaryl, heteroarylalkyl, heterocyclyl, heterocylylalkyl groups respectively, as defined above, attached to an oxygen atom.

The term “acyl” used herein, either alone or in combination with other radicals, refers to a radical containing one to eight carbons such as formyl, acetyl, propanoyl, butanoyl, iso-butanoyl, pentanoyl, hexanoyl, heptanoyl, benzoyl and the like, which may be substituted.

The term “acyloxy” used herein, either alone or in combination with other radicals, refers to a radical acyl, as defined above, directly attached to an oxygen atom, such as acetyloxy, propionyloxy, butanoyloxy, iso-butanoyloxy, benzoyloxy and the like.

The term “acylamino” used herein, either alone or in combination with other radicals, denotes an acyl group as defined earlier attached to an amino group and may be CH₃CONH, C₂H₅CONH, C₃H₇CONH, C₄H₉CONH, C₆H₅CONH and the like, which may be substituted.

The term “mono-substituted amino” used herein, either alone or in combination with other radicals, represents an amino group, substituted with one group selected from (C₁-C₆)alkyl, substituted alkyl, aryl, substituted aryl or arylalkyl groups. Examples of monoalkylamino group include methylamine, ethylamine, n-propylamine, n-butylamine, n-pentylamine and the like and may be substituted.

The term “disubstituted amino” used herein, either alone or in combination with other radicals, denotes an amino group, substituted with two radicals that may be same or different selected from (C₁-C₆)alkyl, substituted alkyl, aryl, substituted aryl, or arylalkyl groups, such as dimethylamino, methylethylamino, diethylamino, phenylmethyl amino and the like and may be substituted.

The term “arylamino” used herein, either alone or in combination with other radicals, refers to an aryl group, as defined above, linked through amino having a free valence bond from the nitrogen atom, such as phenylamino, naphthylamino, N-methyl anilino and the like and may be substituted.

The term “aralkylamino” used herein, either alone or in combination with other radicals, denotes an arylalkyl group as defined above linked through amino having a free valence bond from the nitrogen atom e.g. benzylamino, phenethylamino, 3-phenylpropylamino, 1-napthylmethylamino, 2-(1-napthyl)ethylamino and the like and may be substituted.

The term “oxo” or “carbonyl” used herein, either alone (—C═O—) or in combination with other radicals, such as “alkylcarbonyl”, represents a carbonyl radical (—C═O—) substituted with an alkyl radical such as acyl or alkanoyl, as described above.

The term “carboxylic acid” used herein, alone or in combination with other radicals, denotes a —COOH group, and includes derivatives of carboxylic acid such as esters and amides. The term “ester” used herein, alone or in combination with other radicals, denotes —COO— group, and includes carboxylic acid derivatives, where the ester moieties are alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, and the like, which may be substituted; aryloxycarbonyl group such as phenoxycarbonyl, naphthyloxycarbonyl, and the like, which may be substituted; aralkoxycarbonyl group such as benzyloxycarbonyl, phenethyloxycarbonyl, napthylmethoxycarbonyl, and the like, which may be substituted; heteroaryloxycarbonyl, heteroaralkoxycarbonyl, wherein the heteroaryl group, is as defined above, which may be substituted; heterocyclyloxycarbonyl, where the heterocyclic group, as defined earlier, which may be substituted.

The term “amide” used herein, alone or in combination with other radicals, represents an aminocarbonyl radical (H₂N—C═O—), wherein the amino group is mono- or di-substituted or unsubstituted, such as methylamide, dimethylamide, ethylamide, diethylamide, and the like. The term “aminocarbonyl” used herein, either alone or in combination with other radicals, with other terms such as “aminocarbonylalkyl”, “n-alkylaminocarbonyl”, “N-arylaminocarbonyl”, “N,N-dialkylaminocarbonyl”, “N-alkyl-N-aryl aminocarbonyl”, “N-alkyl-N-hydroxyaminocarbonyl”, and “N-alkyl-N-hydroxyaminocarbonylalkyl”, substituted or unsubstituted. The terms “N-alkylaminocabonyl” and “N,N-dialkylaminocarbonyl” denotes aminocarbonyl radicals, as defined above, which have been substituted with one alkyl radical and with two alkyl radicals, respectively. Preferred are “lower alkylaminocarbonyl” having (C₁-C₆) lower alkyl radicals as described above attached to aminocarbonyl radical. The terms “N-arylaminocarbonyl” and “N-alkyl-N-arylaminocarbonyl” denote amiocarbonyl radicals substituted, respectively with one aryl radical, or one alkyl and one aryl radical. The term “aminocarbonylalkyl” includes alkyl radicals substituted with aminocarbonyl radicals.

The term “hydroxyalkyl” used herein, either alone or in combination with other radicals, refers to an alkyl group, as defined above, substituted with one or more hydroxy radicals, such as hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl and the like.

The term “aminoalkyl” used herein, alone or in combination with other radicals, denotes an amino (—NH₂) moiety attached to an alkyl radical, as defined above, which may be substituted, such as mono- and di-substituted aminoalkyl. The term “alkylamino” used herein, alone or in combination with other radicals, denotes an alkyl radical, as defined above, attached to an amino group, which may be substituted, such as mono- and di-substituted alkylamino.

The term “alkoxyalkyl” used herein, alone or in combination with other radicals is intended to include an alkoxy group, as defined above, attached to an alkyl group, such as methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl and the like. The term “aryloxyalkyl” used herein, alone or in combination with other radicals, includes phenoxymethyl, napthyloxymethyl, and the like. The term “aralkoxyalkyl” used herein, alone or in combination with other radicals, includes C₆H₅CH₂OCH₂, C₆H₅CH₂OCH₂CH₂, and the like.

The term “(C₁-C₁₂)alkylthio” or “(C₁-C₆)alkylthio” used herein, either alone or in combination with other radicals, denotes a straight or branched or cyclic monovalent substituent comprising an alkyl group of one to twelve carbon atoms, as defined above, linked through a divalent sulfur atom having a free valence bond from the sulfur atom, such as methylthio, ethylthio, propylthio, butylthio, pentylthio and the like. Examples of cyclic alkylthio are cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio and the like, which may be substituted.

The term “thio(C₁-C₁₂)alkyl” or “thio((C₁-C₆)alkyl” used herein, either alone or in combination with other radicals, represents an alkyl group, as defined above, attached to a group of formula —SR′, where R′ represents hydrogen, alkyl or aryl group, e.g. thiomethyl, methylthiomethyl, phenylthiomethyl and the like, which may be substituted.

The term “arylthio’ used herein, either alone or in combination with other radicals, refers to an aryl group, as defined above, linked through a divalent sulfur atom, having a free valence bond from the sulfur atom such as phenylthio, napthylthio and the like.

The term “(C₁-C₁₂)alkoxycarbonylamino” used herein, alone or in combination with other radicals, denotes an alkoxycarbonyl group, as defined above, attached to an amino group, such as methoxycarbonylamino, ethoxycarbonylamino, and the like. The term “aryloxycarbonylamino” used herein, alone or in combination with other radicals, denotes an aryloxycarbonyl group, as defined above, attached to the an amino group, such as C₆H₅OCONH, C₆H₅OCONCH₃, C₆H₅OCONC₂H₅, C₆H₄(CH₃O)CONH, C₆H₄(OCH₃)OCONH, and the like. The term “aralkoxycarbonylamino” used herein, alone or in combination with other radicals, denotes an aralkoxycarbonyl group, as defined above, attached to an amino group C₆H₅CH₂OCONH, C₆H₅CH₂CH₂CH₂OCONH, C₆H₅CH₂OCONHCH₃, C₆H₅CH₂OCONC₂H₅, C₆H₄(CH₃)CH₂OCONH, C₆H₄(OCH₃)CH₂OCONH, and the like.

The term “aminocarbonylamino”, “alkylaminocarbonylamino”, “dialkylaminocarboniylamino” used herein, alone or in combination with other radicals, denotes a carbonylamino (—CONH₂) group, attached to amino(NH₂), alkylamino group or dialkylamino group respectively, where alkyl group is as defined above.

The term “alkoxyamino” used herein, alone or in combination with other radicals, denotes an alkoxy group, as defined above, attached to an amino group. The term “hydroxyamino” used herein, alone or in combination with other radicals, denotes —NHOH moiety, and may be substituted.

The term “sulfenyl” or “sulfenyl and its derivatives” used herein, alone or in combination with other radicals, denotes a bivalent group, —SO— or RSO, where R is substituted or unsubstituted alkyl, aryl, heteroaryl, heterocyclyl, and the like.

The term “sulfonyl” or “sulfones and its derivatives” used herein, either alone or in combination with other radicals, with other terms such as alkylsulfonyl, denotes divalent radical —SO₂—, or RSO₂—, where R is substituted or unsubstituted groups selected from alkyl, aryl, heteroaryl, heterocyclyl, and the like. “Alkylsulfonyl” denotes alkyl radicals, as defined above, attached to a sulfonyl radical, such as methylsulfonyl, ethylsulfonyl, propylsulfonyl and the like. The term “arylsulfonyl” used herein, either alone or in combination with other radicals, denotes aryl radicals, as defined above, attached to a sulfonyl radical, such as phenylsulfonyl and the like.

The term “sulfonic acid or its derivatives”, used herein, either alone or in combination with other radicals, represents SO₃H group and its derivatives such as sulfonylamino(SO₂NH₂); N-alkylaminosulfonyl and N,N-dialkylaminosulfonyl radicals where the sulfonylamino group is substituted with one and two alkyl groups respectively, such as N-methylaminosulfonyl, N-ethylaminosulfonyl, N,N-dimethylaminosulfonyl, N-methyl-N-ethylaminosulfonyl and the like; N-arylaminosulfonyl and N-alkyl-N-arylaminosulfonyl groups where the sulfonylamino group is substituted with one aryl radical, or one alkyl and one aryl radical; —SO₃R, wherein ‘R’ represents alkyl, aryl, aralkyl groups, as defined above, which may be substituted.

The term “substituted” used in combination with other radicals, intends to include suitable substituents on that radical such as substituted alkyl, substituted alkenyl, substituted alkynyl, substituted cycloalkyl, substituted aryl, etc, mentioned anywhere in the specification. The suitable substituents include, but are not limited to the following radicals, alone or in combination with other radicals, such as, hydroxyl, oxo, halo, thio, nitro, amino, cyano, formyl, amidino, guanidino, hydrazino, alkyl, haloalkyl, perhaloalkyl, alkoxy, haloalkoxy, perhaloalkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, alkoxy, alkenoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocylyl, heteroaryl, heterocyclylalkyl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, heterocyclylalkoxyacyl, acyl, acyloxy, acylamino, monosubstituted or disubstituted amino, arylamino, aralkylamino, carboxylic acid and its derivatives such as esters and amides, carbonylamino, hydroxyalkyl, aminoalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, arylthio, alkoxycarbonylamino, aryloxycarbonylamino, aralkyloxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino, alkoxyamino, hydroxy amino, sulfenyl derivatives, sulfonyl derivatives, sulfonic acid and its derivatives.

The groups R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, and Ar, may be substituted, where the term “substituted” includes radicals as defined above, or any other group mentioned in the specification.

Some of the above defined terms may occur more than once in the above defined formula (I) and upon such occurrences, each such term may be defined independently of the other.

It is preferred that R⁸ represents (C₁-C₆)alkyl, aralkyl or hydrogen; Z represents O or NH or N(C₁-C₃)alkyl; Y represents O atom; X represents O or S atom; R⁷ represents optionally substituted groups selected from linear or branched (C₁-C₆)alkyl, aralkyl or aryl radical; R⁵ and R⁶ each represent a H atom or R⁵ and R⁶ together may represent a bond; Ar represents a divalent phenyl group or a naphthyl group optionally substituted; W represents O or S atom; n represents all integer 2; R², R³, represent hydrogen, and R¹, R⁴, represent formyl, perhaloalkyl, substituted or unsubstituted groups selected from (C₁-C₆)alkyl, aralkyl, (C₃-C₆)cycloalkyl, aryl, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroaralkyl, alkylthio, arylthio, acyl, alkoxycarbonyl, aryloxycarbonyl, carboxylic acid and its derivatives.

It is more preferred that R⁸ represents (C₁-C₃)alkyl, aralkyl or hydrogen; Z represents O atom; Y represents O atom; X represents O atom; R⁷ represents linear or branched (C₁-C₆)alkyl, optionally substituted with one or more halogen atoms; R⁵ and R¹ represent each a hydrogen atom; Ar represents a divalent phenyl group, optionally substituted with halogen, linear or branched alkyl, linear or branched alkoxy groups; W represents O atom; n represents an integer 2; R², R³ each represent a hydrogen atom and R¹, R⁴ may be same or different and represent optionally substituted groups selected from (C₁-C₆)alkyl, especially, (C₁-C₄)alkyl such as methyl, ethyl, propyl, butyl groups; aralkyl groups such as benzyl, phenethyl; hydroxyalkyl especially hydroxymethyl; aminoalkyl especially aminomethyl; aryl, especially, phenyl optionally substituted with one or more groups such as halo, nitro, cyano, alkyl, alkenyl, phenyl, alkoxy, 1,2-methylenedioxy, heterocyclylalkyl, heteroaralkyl, aryloxy, aralkyl, alkylthio, thioalkyl, hydroxy, alkylcarbonyloxy, halogen, amino, acylamino alkylamino, acyl, acyloxy, alkylsulfinyl, alkylsulfonyl, arylthio, alkylthio, arylsulfenyl, arylsulfonyl, carboxylic acid and its derivatives; heterocyclyl, (C₃-C₆)cycloalkyl groups; optionally substituted heteroaryl group especially, furyl, thienyl, quinolyl, benzofuryl, benzothienyl, pyridyl groups; Alternatively, R¹, R², R³ represent hydrogen atom and R⁴ represent optionally substituted groups selected from aryl, 1,2-methylenedioxyphenyl, heteroaryl, such as furyl, pyridyl, thienyl, benzofuranyl, benzothiophenyl, and the like; (C₁-C₄)alkyl, alkylthio, alkoxy, and acyl groups.

Pharmaceutically acceptable salts forming part of this invention are intended to define but not limited to salts of the carboxylic acid moiety such as alkali metal salts like Li, Na, and K salts; alkaline earth metal salts like Ca and Mg salts; salts of organic bases such as lysine, arginine, guanidine and its derivatives, which may be optionally substituted, diethanolamine, choline, tromethamine and the like; ammonium or substituted ammonium salts and aluminium salts. Salts may be acid addition salts which defines but not limited to sulfates, bisulfates, nitrates, phosphates, perchlorates, borates, hydrohalides, acetates, tartrates, maleiates, fumarates, maleates, citrates, succinates, palmoates, methanesulfonates, benzoates, salicylates, hydroxynaphthoates, benzenesulfonates, ascorbates, glycerophosphates, ketoglutarates and the like. Pharmaceutically acceptable solvates may be hydrates or comprising other solvents of crystallization such as alcohols.

Particularly useful compounds according to the present invention includes

-   [(2R)—N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamide -   [(2S)—N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamide -   (±)     3-{4-[2-(2,4-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(2,4-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(2,4-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters, -   (−) 3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(2-acetylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(2-acetylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(2-acetylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-propylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-propylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-propylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-n-butylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-n-butylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-n-butylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanioic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(3-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(3-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(3-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts; -   (±)     3-{4-[2-(5-methyl-2-(2-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(2-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(2-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-bromophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-bromophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-bromophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-chlorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-chlorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-chlorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(4-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(4-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(4-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2,3-diphenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2,3-diphenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2,3-diphenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(2,5-diisopropylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(2,5-diisopropylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(2,5-diisopropylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-isopropyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-isopropyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-isopropyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(2-methylthiopyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(2-methylthiopyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters, -   (−)     3-{4-[2-(2-methylthiopyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(2,5-diethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(2,5-diethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(2,5-diethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-ethyl-2-(2-phenylethyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-ethyl-2-(2-phenylethyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-ethyl-2-(2-phenylethyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(3-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(3-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(3-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(5-methyl-2-cyclohexyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-cyclohexyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(5-methyl-2-cyclohexyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(5-methyl-2-biphenyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(5-methyl-2-biphenyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(5-methyl-2-biphenyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(5-methyl-2-(5-methyl     furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(5-methyl-2-(5-methyl     furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(5-methyl-2-(5-methyl     furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(5-methyl-2-(4-methyl     phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(5-methyl-2-(4-thiomethyl     phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(5-methyl-2-(4-thiomethyl     phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-cyanophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-cyanophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-cyanophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2′]bipyrrolyl-1-yl])ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)     1′H-[2,2′]bipyrrolyl-1-yl])ethoxy]phenyl}-2-ethoxypropanoic acid and     its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2′]bipyrrolyl-1-yl])ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts; -   (−)     3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-phenylsulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-phenylsulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-phenylsulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(2-benzoyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(2-benzoyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(2-benzoyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(5-methyl-2-cyclopropyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(5-methyl-2-cyclopropyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(5-methyl-2-cyclopropyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(benzofuran-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(benzofuran-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(benzofuran-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(3-carboxymethyl-2-methyl-5-phenyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(3-carboxymethyl-2-methyl-5-phenyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(3-carboxymethyl-2-methyl-5-phenyl     pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its     pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(Benzo[1,3]dioxol-5-yl-)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(Benzo[1,3]dioxol-5-yl-)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(Benzo[1,3]dioxol-5-yl-)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(3-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(3-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(3-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(3,5-dimethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(3,5-dimethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(3,5-dimethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±) 3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+) 3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−) 3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(2,3-dimethyl-5-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(2,3-dimethyl-5-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(2,3-dimethyl-5-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (±)     3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (+)     3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (−)     3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic     acid and its pharmaceutically acceptable salts and its esters; -   (E/Z)     3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxyprop-2-enoic     acid and its pharmaceutically acceptable salts and its esters; -   (E)     3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxyprop-2-enoic     acid and its pharmaceutically acceptable salts and its esters; -   (Z)     3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxyprop-2-enoic     acid and its pharmaceutically acceptable salts and its esters.

The signs (+) and (−) in the beginning of the name or number of a compound intends to denote the dextrorotatory or laevorotatory isomers of the compound. They may contain only one optical isomer or varying amounts of the other optical isomer, keeping the net sign of rotation of plane polarised light (+) or (−) as the case may be. The sign (±) in the beginning of the name or number of a compound intends to indicate a racemic mixture of the two enantiomers with almost zero net rotation of the plane polarized light. The term “and its esters” includes the ester derivative of the carboxylic acid as defined earlier, preferably methyl or ethyl esters. The present invention encompasses the use of not only the compounds of present invention described in formula (I) but also the metabolic products of these compounds formed in vivo for the treatment of diseases mentioned anywhere in the specification.

The present invention also provides methods for the preparation of novel compounds described in the general formula (I), their tautomeric forms, their derivatives, their analogs, their stereoisomers, their pharmaceutically acceptable salts and their pharmaceutically acceptable solvates, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, W, X, Y, Z, Ar and n are as defined earlier. These methods are described below, comprising:

Route 1:

The reaction of a compound of general formula (1a), wherein all symbols are as defined earlier with a compound of formula (1b) which may be optically active or racemic, wherein all symbols are as defined earlier to yield a compound of general formula (I) may be carried out using Paal-Knorr cyclization (Paal C. Ber., 1885, 18, 367; Knorr, L., Ber., 1885, 18, 299). The reaction may be carried out neat or in the presence of a solvent or a mixture thereof such as tetrahydrofuran, hexane, cyclohexane, toluene, methanol, ethanol, heptane, petroleum ether, xylene, benzene, ethyl acetate, tert-butyl acetate, 1,2-dichloroethane, iso-propanol, dioxane, cyclohexane, acetonitrile and the like. The reaction temperature may range from 0° C. to the reflux temperature of the solvent(s) used. The water produced may be removed by using a Dean Stark water separator or by water scavengers such as molecular sieves. The reaction may be carried out in the absence or presence of an inert atmosphere such as N₂, He or Ar. The reaction may be carried out under acidic condition provided by acids like acetic acid, propanoic acid, butyric acid, isobutyric acid, pivalic acid, p-toluenesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, trifluoroacetic acid, chloroacetic acid, chloropropanoic acid, phenylacetic acid, phenylpropanoic acid, malonic acid, succinic acid, benzoic acid, halogenated benzoic acid, toluic acid and the like. Mineral acids such as HCl or HBr may also be used. The reaction time may range from 5 minutes to 72 hours, preferably from 1 to 48 hours.

Route 2:

The reaction of compound of formula (1c), where all symbols are as defined earlier and L¹ represents a leaving group such as halogen atom, p-toluenesulfonate, methanesulfonate, trifluoromethanesulfonate and the like with a compound of formula (1d) which may be optically active or racemic, where W is either O or S and all other symbols are as defined earlier, to produce a compound of general formula (I). This reaction may be carried out in the presence of solvents such as acetone, tetrahydrofuran, dimethylsulfoxide, dioxane, acetonitrile, dimethyl formamide, DME, benzene, toluene, pet. ether, heptane, hexane, 2-butanone, xylene, alcohols such as methanol, ethanol, propanol, butanol, iso-butanol, tert-butanol, pentanol and the like or a mixture thereof. Base such as alkali metal carbonate such as K₂CO₃, Na₂CO₃, CsCO₃, and the like; or alkali metal hydroxide such as NaOH, KOH and the like, may be used during this reaction. Alkali metal hydrides such as NaH, KH can be used whenever solvent employed is not protic or contain carbonyl group. The reaction may be carried out at a temperature in the range 0° C. to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours.

Route 3:

The reaction of compound of general formula (1e) where all symbols are as defined earlier and W represents oxygen atom, with a compound of general formula (1d) which may be optically active or racemic, where W is O or S and all other symbols are as defined earlier may be carried out using coupling agents such as DCC, EDC, triaryl phosphine/dialkyl azadicarboxylate such as PPh₃/DEAD or PPh₃/DIAD and the like. Inert atmosphere may be maintained using N₂, Ar or He. Solvents such as tetrahydrofuran, dioxane, DME, toluene, dichloromethane, chloroform, carbon tetrachloride, acetonitrile and the like may be used. Compounds such as 4-dimethylaminopyridine, hydroxybenzotriazole etc. may be used in the range of 0.05 to 2 equivalents. The reaction temperature in the range of 0° C. to reflux temperature of the solvent may be used, preferably, 20 PC to 80° C. The duration of the reaction may range from 0.5 to 24 h, preferably 0.5 to 12 hours.

Route 4:

The reaction of a compound of general formula (1h) wherein all the symbols are as defined earlier, with a compound of formula (1i), where all the symbols are as defined earlier and R represents (C₁-C₈) alkyl to afford a compound of formula (I) where R⁵ and R⁶ represent a bond and all other symbols are as defined earlier, may be carried out under Wittig Horner reaction conditions in the presence of a base such as alkali metal hydrides, like NaH or KH, alkali metal alkoxides such as NaOMe, NaOEt, K⁺t-BuO⁻ or mixture thereof, organolithiums like CH₃Li, BuLi, sec-BuLi, LDA and the like. Aprotic solvents such as THF, dioxane, DMF, DMSO, DME and the like or mixture thereof may be employed. HMPA favours the progression of the reaction but not essential. The reaction may be carried out at a temperature ranging from −80° C. to 100° C., preferably from 0° C. to 30° C. The reaction proceeds more effectively under anhydrous and inert conditions.

The compound of formula (I) where R⁵ and R⁶ represent a bond may be reduced to a compound of general formula (I) where R⁵ and R⁶ each represent hydrogen atom by reacting with hydrogen gas in the presence of a catalyst such as 5-10% Pd/C, Rh/C, Pt/C Raney Ni and the like, 5-100% w/w of the catalyst may be employed or the mixture thereof. The pressure of hydrogen gas may be one atmosphere to 80 psi. Suitable solvents are alcohols such as ethanol, methanol and the like, ethyl acetate, THF, dioxane, acetic acid and the like. Temperature may be in the range of 20° C. to 80° C., may be used for this reduction process. Metal-solvent such as magnesium in alcohol or sodium amalgam in alcohol may also be used, for this reduction process.

According to a feature of the present invention, there is provided an intermediate of formula (1h),

wherein R² and R³ represent hydrogen, and R¹, R⁴ may be same or different, and represent hydrogen, haloalkyl, perhaloalkyl, nitro, cyano, formyl, or substituted or unsubstituted groups selected from linear or branched (C₁-C₆)alkyl, linear or branched (C₂-C₆)alkenyl, linear or branched (C₂-C₆)alkynyl, (C₃-C₇)cycloalkyl, (C₃-C₇)cycloalkenyl, aryl, aralkyl, heterocyclyl, heteroaryl, heterocyclyl(C₁-C₆)alkyl, heteroar(C₁-C₆)alkyl, acyl, acyloxy, carboxylic acid and its derivatives such as esters and amides, hydroxyalkyl, aminoalkyl, mono-substituted or di-substituted aminoalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, (C₁-C₆)alkylthio, thio(C₁-C₆)alkyl, arylthio, derivatives of sulfenyl and sulfonyl groups, sulfonic acid and its derivatives; n represents an integer 2, W represents O, S or NR⁹, where R⁹ represents hydrogen, (C₁-C₆)alkyl or aryl groups; Ar represents a substituted or unsubstituted divalent single or fused aromatic, heteroaromatic group;

According to another feature of the present invention, there is provided a process for the preparation of intermediate of the general formula (1h) as defined earlier which comprises reacting a compound of general formula (1c),

wherein, R¹-R⁴, n are as defined earlier and L¹ is a halogen atom such as chlorine, bromine or iodine or a leaving group such as methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate and the like with the compound of the formula (1j), where Ar and W are as defined earlier.

The reaction of the compound of formula (1c) with the compound of formula (1j) to produce a compound of formula (1h) may be carried out in the presence of solvents such as acetone, THF, DMSO, dioxane, 2-butanone, acetonitrile, DMF, DME, benzene, toluene, xylene, alcohols such as methanol, ethanol, propanol, butanol, isobutanol, tert-butanol, pentanol and the like or a mixture thereof. Bases such as alkali metal carbonates such as K₂CO₃, Na₂CO₃, CsCO₃ and the like may be used; alkali metal hydroxides like NaOH, KOH and the like; or mixtures thereof may be used. Alkali metal hydrides such as NaH, KH and the like, may be used in cases when the solvent used is not protic and does not contain carbonyl group. The reaction temperature may range from 20° C. to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours. The inert atmosphere may be maintained by using inert gases such as N₂, Ar or He.

Alternatively, the intermediate of the general formula (1h), can also be prepared by the reaction of compound of general formula (1e),

wherein R¹-R⁴, n and W are as defined earlier and with a compound of the formula (1k), where Ar is as defined earlier and L² is a halogen atom such as fluorine, chlorine, bromine or iodine. The reaction of the compound of formula (1e) with the compound of formula (1k) to produce a compound of formula (1h) may be carried out in the presence of solvents such as THF, DMF, DMSO, DME and the like. Mixture of solvents may be used. The inert atmosphere may be maintained by using inert gases such as N₂, Ar or He. The reaction may be effected in the presence of a base such as K₂CO₃, Na₂CO₃, NaH or mixtures thereof. The reaction temperature may range from 20° C. to 150° C., preferably at a temperature in the range from 30° C. to 100° C. The duration of reaction may range from 1 to 24 hours, preferably from 2 to 6 hours.

The reaction of compound of general formula (1e) wherein W represents O and all other symbols are as defined earlier with the compound of formula (1j) may be carried out using suitable coupling agents such as dicyclohexyl urea, triarylphosphine/dialkylazadicarboxylate such as PPh₃/DEAD and the like. The reaction may be carried out in the presence of solvents such as THF, DME, CH₂Cl₂, CHCl₃, toluene, acetonitrile, carbontetrachloride and the like. The inert atmosphere may be maintained by using inert gases such as N₂, Ar or He. The reaction may be effected in the presence of DMAP, HOBT and they must be used in the range of 0.05 to 2 equivalents, preferably 0.25 to 1 equivalents. The reaction temperature may range from 0° C. to 100° C., preferably at a temperature in the range from 20° C. to 80° C. the duration of reaction of the reaction may range from 0.5 to 24 hours, preferably from 6 to 12 hours.

In another embodiment of this invention, there is provided a process for the preparation of a compound of the general formula (1c), which comprises reacting the compound of general formula (1a) wherein R¹-R⁴ are as defined earlier,

with substituted amino compound (1m), where all symbols are is as defined earlier, to yield the intermediate of the general formula (1c).

In yet another embodiment of this invention, there is provided a process for the preparation of a compound of the general formula (1e), which comprises reacting the compound of general formula (1a) wherein R¹-R⁴ are as defined earlier,

with substituted amino compound (1l), where all symbols are is as defined earlier, to yield the intermediate of the general formula (1e).

The reactions of a compound of general formula (1a) with a compound of general formula (1l) or a compound of general formula (1m) may be carried out neat or in presence of solvents or a mixture thereof such as tetrahydrofuran, hexane, toluene, methanol, ethanol, heptane, petroleum ether, xylene, benzene, ethyl acetate, tert-butyl acetate, 1,2-dichloroethane, iso-propanol, tert-butanol, dioxane, cyclohexane, acetonitrile and the like. The reaction temperature may range from 0° C. to the reflux temperature of the solvent(s) used. The water produced may be removed by using a Dean Stark water separator or by water scavengers such as molecular sieves. The reaction may be carried out in the presence of an inert atmosphere such as N₂, He or Ar. The reaction may be carried out in the presence of an acid, such as acetic acid, propanoic acid, butyric acid, isobutyric acid, pivalic acid, p-toluenesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, trifluoroacetic acid, chloroacetic acid, chloropropanoic acid, phenylacetic acid, phenylpropanoic acid, malonic acid, succinic acid, benzoic acid, halogenated benzoic acid, toluic acid and the like.

In yet another embodiment of this invention, there is provided an alternate process for the preparation of a compound of the general formula (1c), which comprises reacting the compound of general formula (1n) wherein R¹-R⁴ are as defined earlier,

with the compound of formula (1o) where L₁ and L₂ may be same or different and represent leaving groups such as halogen atom as Cl, Br, or I, methanesulfonate, p-toluenesulfonate and the like; and n as defined earlier.

In yet another embodiment of this invention, there is provided an alternate process for the preparation of a compound of the general formula (1e), which comprises reacting the compound of general formula (1n) where R¹-R⁴ are as defined earlier,

with the compound of formula (1p) where L₂ represent leaving groups such as halogen atom as Cl, Br, or I, methanesulfonate, p-toluenesulfonate and the like; and n as defined earlier.

The reaction of compound of general formula (1n), with either (1o) or (1p) may be carried out in solvents such as alcohol like methanol, ethanol, iso-propanol and the like; THF, dioxane, DMSO, DMF, acetonitrile, heptane, benzene, toluene, xylene and the like. The reaction may be carried out in presence of bases such as NaH, KH, Na₂CO₃, K₂CO₃, NaOH, KOH, LiNH₂, NaNH₂ and the like. Phase transfer catalyst such as tetrabutyl ammonium halide, tetrabutyl ammonium hydroxide (TBAH) and the like may be used. The reaction temperature may range from 0° C. to the reflux temperature of the solvent employed. The reaction may be carried out in the presence of an inert atmosphere such as N₂, He or Ar.

In another embodiment of this invention, there is provided a process for the preparation of a compound of the general formula (1e), wherein R¹-R⁴ and n are as defined earlier and W represents O, which comprises reducing the corresponding acid

The reduction of compound of general formula (1q) may be carried out in presence of solvents or a mixture thereof such as tetrahydrofuran, dioxane, ether and the like. The reaction temperature may range from 0° C. to the reflux temperature of the solvent(s) used. The reaction may be carried out in the presence of an inert atmosphere such as N₂, He or Ar. Suitable reducing agent such as sodium borohydride/iodine, diborane and its derivative, LiAlH₄ and the like may be used.

The compound of general formula (1q) may be prepared by the reaction of compound of general formula (1n) with a compound of L₁(CH₂)_(n-1)COOR, where L₁ and R are as defined earlier, followed by hydrolysis of the ester group to acid using methods commonly used.

The compounds of the present invention have asymmetric centers and occur either as racemates or racemic mixtures as well as individual diastereomers of any of the possible isomers, including optical isomers, being included in the present invention The stereoisomers of the compounds of the present invention may be prepared by one or more ways presented below:

-   i. One or more of the reagents may be used in their single isomeric     form. For example, compound (1b) or (1d) may be pure stereoisomers. -   ii. Optically pure catalysts or chiral ligands along with metal     catalysts may be employed in the reduction process. The metal     catalyst may be Rhodium, Ruthenium, Indium and the like. The chiral     ligands may preferably be chiral phosphines. (Principles of     Asymmetric synthesis J E Baldwin Ed. Tetrahedron series, Volume 14,     Page no. 311-316) -   iii. Mixture of stereoisomers may be resolved by conventional     methods such as microbial resolution, resolving the diastereomeric     salts formed with chiral acids or chiral bases. Chiral acids may be     tartaric acid, mandelic acid, lactic acid, camphorsulfonic acid,     amino acids and the like. Chiral bases may be cinchona alkaloids,     (+) or (−) brucine, α-methyl benzylamine, (+) or (−) phenyl     glycinol, ephedrine, amino sugars such as glucosamines or a basic     amino acid such as lysine, arginine and the like. -   iv. Resolution of the mixture of stereoisomers may also be effected     by chemical methods by derivatization of the compound with a chiral     compound such as chiral amines, chiral acids, chiral amino alcohols,     amino acids into a 1:1 mixture of diastereomers and the     diastereomers may be separated by conventional methods of fractional     crystallization, chromatography and the like followed by cleaving     the derivative (Jaques et al. “Enantiomers, Racemates and     Resolution”, Wiley Interscience, 1981; R. A. Sheldon, in     “Chirotechnology”, Marcel Dekker, Inc. NY, Basel, 1993, 173-204 and     references therein; A. N. Collins, G. N. Sheldrack and J Crosby, in     “Chirality in Industry II”, John Wiley & Sons, Inc, 1997, 81-98 and     references therein; E. L. Eliel and S. H. Wilen, in “Stereochemistry     of Organic Compound”, John Wiley & Sons, Inc, 1999, 297-464 and     references therein.)

It will be appreciated that in any of the above mentioned reactions any reactive group in the substrate molecule may be protected, according to conventional chemical practice. Suitable protecting groups in any of the above mentioned reactions are those used conventionally in the art. The methods of formation and removal in such protecting groups are those conventional methods appropriate to the molecule being protected. T. W. Greene and P. G. M. Wuts “Protective groups in Organic Synthesis”, John Wiley & Sons, Inc, 1999, 3^(rd) Ed., 201-245 along with references therein.

It will be appreciated that the above-mentioned preparation of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, and/or pharmaceutically acceptable solvate thereof is a stereoselective procedure and that the compound of formula (I) is a single stereoisomer. Favorably, a compound of formula (I) is present in admixture with less than 50% w/w of its racemic isomer, suitably 80-100% and preferably 90-100% pure, such as 90-95%, most preferably 95-100%, for example 95%, 96%, 97%, 98%, 99% and 99.99% optically pure.

Preferably the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, and/or pharmaceutically acceptable solvate thereof is in optically pure form.

The absolute stereochemistry of the compounds may be determined using conventional methods, such as X-ray crystallography.

The pharmaceutically acceptable salts forming a part of this invention may be prepared by treating the compound of formula (I) with 1-6 equivalents of a base such as sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium tert-butoxide, calcium hydroxide, calcium acetate, calcium chloride, magnesium hydroxide, magnesium chloride, magnesium alkoxide and the like. Solvents such as water, acetone, ether, THF, methanol, ethanol, t-butanone, 2-butanone, dioxane, propanol, butanol, isopropanol, diisopropyl ether, tert-butyl ether or mixtures thereof may be used. Organic bases such as lysine, arginine, methyl benzylamine, ethanolamine, diethanolamine, tromethamine, choline, guanidine and their derivatives may be used. Acid addition salts, wherever applicable may be prepared by treatment with acids such as tartaric acid, mandelic acid, fumaric acid, malic acid, lactic acid, maleic acid, salicylic acid, citric acid, ascorbic acid, benzene sulfonic acid, p-toluene sulfonic acid, hydroxynaphthoic acid, methane sulfonic acid, acetic acid, benzoic acid, succinic acid, palmitic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and the like in solvents such as water, alcohols, ethers, ethyl acetate, dioxane, THF, acetonitrile, DMF or a lower alkyl ketone such as acetone, or mixtures thereof.

Another aspect of the present invention comprises a pharmaceutical composition, containing at least one of the compounds of the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates thereof as an active ingredient, together with pharmaceutically employed carriers diluents and the like.

Pharmaceutical compositions containing a compound of the present invention may be prepared by conventional techniques, e.g. as described in Remington: the Science and Practice of Pharmacy, 19^(th) Ed., 1995. The compositions may be in the conventional forms, such as capsules, tablets, powders, solutions, suspensions, syrups, aerosols or topical applications. They may contain suitable solid or liquid carriers or in suitable sterile media to form injectable solutions or suspensions. The compositions may contain 0.5 to 20%, preferably 0.5 to 10% by weight of the active compound, the remaining being pharmaceutically acceptable carriers, excipients, diluents, solvents and the like.

Typical compositions containing a compound of formula (I) or a pharmaceutically acceptable acid addition salt thereof, associated with a pharmaceutically acceptable excipients which may be a carrier or a diluent or be diluted by a carrier, or enclosed within a carrier which can be in the form of a capsule, sachet, paper or other container. When the carrier serves as a diluent, it may be a solid, semi-solid, or liquid material, which acts as a vehicle, excipients or medium for the active compound. The active compound can be absorbed on a granular solid container for example in a sachet. Some of suitable carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alkyl, sucrose, cyclodextrin, amylose, magnesium sterate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acids monoglycerides and diglycerides, pentaerythritol fatty acids esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone. Similarly, the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The formulations may also include wetting agents, emulsifying and suspending agents, preservatives, sweetening agents or flavoring agents. The formulations of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the patient by employing procedures well known in the art.

The pharmaceutical compositions can be sterilized and mixed, if desired, with auxiliary agents, emulsifiers, buffers and/or coloring substances and the like, which do not deleteriously react with the active compounds.

The route of administration may be any route, which effectively transports the active drug to the appropriate or desired site of action effectively, such as oral, nasal, transdermal, pulmonary or parental e.g. rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic solution or an ointment, preferably through oral route.

If a solid carrier is used for oral administration, the preparation may be tabletted, placed in a hard gelatin capsule in powder or pellet form or it can be in the form of a troche or lozenge. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatin capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution.

For nasal administration, the preparation may contain a compound of formula (I) dissolved or suspended in a liquid carrier, in particular an aqueous carrier, for aerosol application. The carrier may contain additives such as solubilizing agent, e.g. propylene glycol, surfactants, absorption enhancers such as lecithin (phosphatidylcholine) or cyclodextrin, or preservatives such as parabens.

For parental application, particularly suitable are injectable solutions or suspensions, preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil.

Tablet, dragees or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application. Preferably, carriers for tablets, dragees or capsules include lactose, corn starch and/or potato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be employed.

A typical tablet which may be prepared by conventional tabletting techniques may contain:

Core:

Active compound (as free compound or salt thereof) 5.0 mg Colloidal silicon dioxide 1.5 mg Cellulose, misrocrytalline 70.0 mg  Modified cellulose gum 7.5 mg Magnesium sterate ad. Coating: HPMC approx 9.0 mg *Mywacett 9-40 T approx. 0.9 mg *Acylated monoglyceride used as plasticizer for film coating.

The compounds of general formula (I) or the compositions thereof are useful for the treatment and/or prophylaxis of disease caused by metabolic disorders such as hyperlipidemia, insulin resistance, Leptin resistance, hyperglycemia, obesity, or inflammation.

These compounds are useful for the treatment of hypercholesteremia, familial hypercholesteremia, hypertriglyceridemia, type 2 diabetes, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, insulin resistance, coronary heart disease, atherosclerosis, xanthoma, stroke, peripheral vascular diseases and related disorders, diabetic complications, certain renal diseases such as glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, retinopathy, nephropathy, psoriasis, polycystic ovarian syndrome, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, arteriosclerosis, Xanthoma, pancreatitis and for the treatment of cancer.

The compounds of the invention may be administered to a mammal, especially, a human in need of such treatment, prevention, elimination, alleviation or amelioration of diseases mentioned above.

The compounds of the present invention are effective over a wide dosage range, however, the exact dosage, mode of administration and form of composition depends upon the subject to be treated and is determined by the physician or veterinarian responsible for treating the subject. Generally, dosages from about 0.025 to about 200 mg preferably from about 0.1 to about 100 mg, per day may be used. Generally, the unit dosage form comprises about 0.01 to 100 mg of the compound of formula (I), as an active ingredient together with a pharmaceutically acceptable carrier. Usually suitable dosage forms for nasal, oral, transdermal or pulmonary administration comprises from about 0.001 mg to about 100 mg, preferably from 0.01 mg to about 50 mg of the active ingredient mixed with a pharmaceutically acceptable carrier or diluent.

In another aspect of the present invention, method of treatment and/or prevention of the diseases mentioned above are provided.

In a further aspect of the present invention, use of one or more compounds of the general formula (I) or pharmaceutically acceptable salts, for the preparation of a medicament thereof for the treatment and/or prevention of diseases mentioned in this document is provided.

In still further aspect of the present invention use of the compounds of the present invention alone or in combination with statins, glitazones, biguanides, angiotensin II inhibitors, aspirin, insulin secretagogue, β-sitosterol inhibitor, sulfonylureas, insulin, fibric acid derivatives, nicotinic acid, cholestyramine, cholestipol or probucol, α-glycosidase inhibitors or antioxidants, which may be administered together or within such a period as to act synergistically together.

The invention is explained in detail by the examples given below, which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.

¹H NMR spectral data given in the tables (vide infra) are recorded using a 300 MHz spectrometer (Bruker AVANCE-300) and reported in δ scale. Until and otherwise mentioned the solvent used for NMR is CDCl₃ using Tetramethyl silane as the internal standard.

PREPARATION 1 Preparation of 1-(2-hydroxyethyl)-5-ethyl-2phenyl-1H-pyrrole (Compound No. 17)

A mixture of 1-phenyl-hexane-1,4-dione (5 g), ethanol amine (1.6 g) and pivalic acid (2.15 g) in a solvent mixture containing n-heptane:tetrahydrofuran:toluene (4:1:1, 50 mL) was refluxed with stirring at 110-120° C. Water formed during the reaction was removed azeotropically during 3 to 4 hrs. The reaction mixture was cooled and the solvent was removed. The residue obtained was dissolved in dichloromethane (50 mL), washed with saturated sodium bicarbonate solution (50 mL), water (50 mL), and then with brine (50 mL), dried (Na₂SO₄) and the solvent was evaporated. The crude compound obtained as an oily mass. The crude substance was used in the next step without purification.

In the like manner to that described in Preparation 1, the following compounds of general formula (1e) were prepared from the appropriately substituted diketones as mentioned in Table 1. The latter can be synthesized by using various routes found in literature.

TABLE 1 (1e)

Comp. Substituents on the pyrrole ring in (1e) No. R¹ R² R³ R⁴ 1. CH₃ H H CH₂CH₃ Mol. Wt. = 153 Yield= 53% ¹H: 1.26 (3H, J=7.4Hz); 2.22 (3H, s); 2.56 (2H, q, J=7.4Hz); 3.71 (2H, t, J=5.86Hz); 3.88 (2H, t, J=5.89Hz); 5.79-5.81 (2H, m). 2. CH₃ H H (CH₂)₂CH₃ Mol. Wt. = 167 Yield = 36% ¹H: 1.02 (3H, t, J=7Hz); 1.65 (2H, m); 2.25 (3H, s); 2.5 (2H, t, J 7.7Hz); 4.1 (2H, t, J=5.9Hz); 4.35 (2H, t, J=5.9 Hz); 5.8-5.82 (2H, m). 3. CH₃ H H (CH₂)₃CH₃ Mol. Wt. = 181 Yield = 58% ¹H: 0.94 (3H, t, J=7.2Hz); 1.36-1.4 (2H, m); 1.58-1.67 (2H, m); 2.22 (3H, s); 2.53 (2H, t, J=7.7Hz); 3.7 (2H, t, J=5.8Hz); 3.89 (2H, t, J=5.8Hz); 5.7-5.8 (2H, m). 4. CH₃ H H

Mol. Wt. = 201 Yield = 62% ¹H: 2.33 (3H, s); 3.5-3.6 (2H, t, J=5.9Hz); 4.05-4.09 (2H, t, J=6.0Hz); 5.95 (1H, d, J=3.3Hz); 6.09 (1H, d, J=3.3Hz); 7.25-7.29 (1H, m); 7.30-7.38 (4H, m). 5. CH₃ H H

Mol. Wt. = 215 Yield = 55% ¹H: 2.32 (3H, s); 2.37 (3H, s); 3.59 (2H, t, J=6.9Hz); 4.10 (2H, t, J=6.9Hz); 5.94 (1H, d, J=3.36Hz); 6.0 (1H, d, J=3.36Hz); 7.2 (2H, d, J=8.5Hz); 7.25 (2H, d, J=8.5Hz) 6. CH₃ H H

Mol. Wt. = 215 Yield = 60% ¹H: 2.32 (3H, s); 2.36 (3H, s); 3.57 (2H, t, J=6Hz); 4.08 (2H, t, J=6.06Hz); 5.94 (1H, d, J=2.28Hz); 6.1 (1H, d, J=3.39Hz); 7.09-7.3 (4H, m). 7. CH₃ H H

Mol. Wt. = 215 Yield = 60% ¹H: 2.32 (3H, s); 2.36 (3H, s); 3.58 (2H, t, J=6Hz); 4.07 (2H, t, J=6.06Hz); 5.94 (1H, d, J=2.28Hz); 6.07 (1H, d, J=3.39Hz); 7.09-7.15 (2H, m); 7.24-7.29 (2H, m). 8. CH₃ H H

Mol. Wt. = 231 Yield = 45% ¹H: 2.3 (3H, s); 3.53 (2H, t, J=6.9Hz); 3.84 (3H, s); 4.0 (2H, t, J=6.9Hz); 5.9 (1H, d, J=3.36Hz); 6.0 (1H, d, J=3.36Hz); 6.95 (2H, d, J=6.78Hz); 7.2 (2H, d, J=6.78Hz). 9. CH₃ H H

Mol. Wt. = 280 Yield = 55% ¹H: 2.32 (3H, s); 3.61-3.63 (2H, m) 4.05 (2H, t, J=6.2Hz); 5.95 (1H, dd); 6.1 (1H, d, J=3.4Hz); 7.25-7.3 (2H, m); 7.47-7.52 (2H, m). 10. CH₃ H H

Mol. Wt. = 219 Yield = 32% ¹H: 2.3 (3H, s); 3.6 (2H, t, J=6.0Hz); 4.05 (2H, t, J=6.0Hz); 5.9 (1H, d, J=2.8Hz); 6.0 (1H, d, J=3.3Hz); 7.04-7.1 (2H, m); 7.26-7.37 (2H, m) 11. CH₃ H H

Mol. Wt. = 235.5 Yield = 61% ¹H: 2.3 (3H, s); 3.6 (2H, t, J=5.9Hz); 4.12 (2H, t, J=5.9Hz); 5.97 (1H, d, J=3.2Hz); 6.10 (1H, d, J=3.2Hz); 7.09-7.37 (4H, m). 12. CH₃ H

Mol. Wt. = 277 Yield = 90% ¹H: 2.37 (3H, s); 3.5 (2H, t, J=6Hz); 3.95 (2H, t, J=6.0Hz); 6.2 (1H, d, J=2.8Hz); 7.1-7.4 (10H, m). 13. i-Pr H H i-Pr Mol. Wt. = 195 Yield = 93% ¹H: 1.21-1.24 (12H, d, J=6.7Hz); 2.91-2.98 (2H, m); 3.77 (1H, t, J=6.2Hz); 4.01 (2H, t, J=6.2Hz); 5.8 (2H, s). 14. i-Pr H H

Mol. Wt. = 229 Yield = 86% ¹H: 1.29 (6H, d, J=6.78Hz); 3.0-3.05 (1H, m); 3.51 (2H, t, J=6.21Hz); 4.12 (2H, t, J=6.25Hz); 6.0 (1H, d, J=3.54Hz); 6.125 (1H, d, J=3.54Hz); 7.27-7.31 (3H, m) 7.37 (2H, m) 15. i-Pr

H

Mol. Wt. = 366 Yield = 45% ¹H: 1.43-1.45 (6H, d, J=7.2Hz); 3.3-3.4 (1H, m); 4.09-4.1 (2H, m); 3.80-3.85 (2H, m); 6.85 (1H, s); 7.0-7.5 (9H, m). 16 —C₂H₅ H H —C₃H₅ Mol. Wt. = 167 Yield = 82% ¹H: 1.26 (6H, t, J=7.4Hz); 2.59 (4H, q, J=7.4Hz); 3.76 (2H, t, J=5.8Hz); 3.93 (2H, t, J=5.9Hz); 5.86 (2H, s) 17 —C₂HD 5 H H

Mol. Wt. = 215 Yield = 82% ¹H: 1.32 (3H, t, J=7.3Hz); 2.68 (2H, q, J=7.6 Hz); 3.57 (2H, t, J=5.9Hz); 4.09 (2H, t, J=5.9Hz); (1H, d, J=3.4Hz); 6.1 (1H, d, J=3.4Hz); 7.28-7.39 (5H, m) 18 —CH₃ H H

Mol. Wt. = 229 Yield = 76% ¹H: 2.23 (3H, s); 2.8-2.9 (2H, m); 2.91-2.99 (2H, m); 3.69 (2H, t, J=5.8Hz); 3.86 (2H, t, J=5.8Hz); 5.83 (1H, d, J=3.3Hz); 5.88 (1H, d, J=3.6Hz); 7.17-7.31 (5H, m) 19 —CH₃ H H

Mol. Wt. = 231 Yield = 80% ¹H: 2.33 (3H, s); 3.64 (2H, t, J=6Hz); 3.82 (3H, s); 4.11 (2H, t, J=6Hz); 5.9 (1H, d, J=3.3Hz); 6.12 (1H, d, J=3.3Hz); 6.8-7.32 (4H, m) 20 —CH₃ H H

Mol. Wt. = 207 Yield = 82% ¹H: 1.24-1.81 (10H, m); 2.23 (3H, s); 2.47-2.52 (1H, m); 3.76-3.78 (2H, m); 3.94 (2H, t, J=6Hz); 5.79-5.83 (2H, m) 21 —CH₃ H H

Mol. Wt. = 277 Yield = 76% ¹H: 2.32 (3H, s); 3.6 (2H, t, J=6Hz); 4.09 (2H, t, J=6Hz); (1H, d, J=2.94Hz); 6.15 (1H, d, J=3.39Hz); 7.2-7-6 (9H, m) 22 —CH₃ H H

Mol. Wt. = 191 Yield = 7O% ¹H: 2.3 (3H, s); 3.81-3.83 (2H, m); 4.17 (2H, t, J=5.8Hz); 5.93 (1H, d, J=3.5Hz); 6.33 (2H, dd, J=3.3Hz, J₂=3.4Hz); 6.43 (1H, dd, J=1.87Hz, 1.88Hz); 7.402-7.407 (1H, m) 23 —CH₃ H H

Mol. Wt. = 205 Yield = 80% ¹H: 2.30 (3H, s); 2.32 (3H, s); 3.85 (2H, t, J=5.77Hz); 4.15 (2H, t, J=5.8Hz); 5.9 (1H, d, J=3.5Hz); 6.0 (1H, d, J=3.43Hz); 6.22 (1H, d, J=3.09Hz); 6.27 (1H, d, J=3.54Hz) 24 —CH₃ H H

Mol. Wt. = 247 Yield = 100% ¹H: 2.3 (3H, s); 2.49 (3H, s); 3.58 (2H, t, J=6.03Hz); 4.0 (2H, t, J=6.0Hz); 5.93-5.94 (1H, dd, J=.738Hz, J₂=0.665Hz); 6.0 (1H, d, J=3.4Hz) 7.22-7.32 (4H, m) 25 —CH₃ H H

Mol. Wt. = 226 Yield = 70% ¹H: 2.34 (3H, s); 3.67 (2H, t, J=5.9Hz); 4.14 (2H, t, J=6Hz); 6.011 (1H, d, J=3.4Hz); 6.23 (1H, d, J=3.5Hz); 7.5 (2H, d, J=8.5Hz); 7.65 (2H, d, J=8.5Hz) 26 —CH₃ H H

Mol. Wt. = 293 Yield = 76% ¹H: 2.33 (3H, s); 3.65 (2H, t, J=6Hz); 4.09 (2H, t, J=6Hz); 5,9 (1H, dJ=3.31Hz); 6.08 (1H, d, J=3.38Hz); 6.99-7.38 (9H, m) 27 —CH₃ H H

Mol. Wt. = 344 Yield = 85% ¹H: 2.28 (3H, s); 2.4 (3H, s); 3.59 (2H, t, J=5.7Hz); 3.74 (2H, t, J=5.7Hz); 5.63 (1H, d, J=3.4Hz); 5.86 (1H, d, J=3.4Hz); 6.25-6.26 (1H, m); 6.31 (1H, t, J=3.3Hz); 7.23 (2H, d, J=8.3Hz); 7.43-7.48 (3H, m) 28 —CH₃ H H

Mol. Wt. = 261 Yield = 100% ¹H: 2.3 (3H, s); 3.65 (2H, t, J=5.9Hz); 3.88 (3H, s); 3.9 (3H, s); 4.06 (2H, t, J=6.0Hz); 5.94-5.95 (1H, m) 6.0 (1H, d, J=3.1Hz); 6.87-7.26 (3H, m) 29 —CH₃ H H

Mol. Wt. = 258 Yield = 78% ¹H: 2.12 (3H, s); 2.3 (3H, s); 3.61 (2H, t, J=6.03Hz); 4.15 (2H, t, J=6.0Hz); 5.9 (1H, d, J=2.7Hz); 6.02 (1H, d, J=3.3Hz); 6.7 (2H, d, J=8.5Hz); 7.16 (2H, d, J=8.5Hz) 30 —CH₃ H H

Mol. Wt. = 328 Yield = 92% ¹H: 1.4-1.63 (6H, m); 2.3 (3H, s); 2.48-2.5 (4H, m); 2.75 (2H, t, J=6.03Hz); 3.5 (2H, t, J=6.2Hz); 4.0 (2H, t, J=6.3Hz); 4.1 (2H, t, J=6.0Hz); 5.91-5.92 (1H, m); 6.0 (1H, d, J=3.3 Hz); 6.889 (2H, d, J=8.5Hz); 7.2 (2H, d, J=8.5Hz) 31 —CH₃ H H

Mol. Wt. = 257 Yield = 83% ¹H: 2.3 (3H, s); 3.6 (2H, t, J=6Hz); 4.03 (2H, t, J=6.1Hz); 4.55 (2H, d, J=5.3Hz); 5.28-5.32 (2H, dd, J=1.35Hz J₂=1.35Hz); 5.40-5.46 (1H, dd, J=1.56Hz, J₂=1.5Hz); 5.93 (1H, d, J=3.36Hz); 6.04 (1H, d, J=3.42Hz); 6.93 (2H, d, J=8.5Hz), 7.28 (2H, d, J=8.5Hz) 32 —CH₃ H H

Mol. Wt. = 309 Yield = 79% ¹H: 2.3 (3H, s); 3.64 (2H, t, J=6Hz); 4.08 (2H t, J=6.09Hz); 5.96 (1H, d, J=3.36Hz); 6.11 (1H, d, J=3.45Hz); 7.25-7.42 (9H, m) 33 —CH₃ H H

Mol. Wt. = 279 Yield = 80% ¹H: 2.35 (3H, s); 2.08 (3H, s) 3.68 (2H, t, J=5.7Hz); 4.17 (2H, t, J=5.8Hz); 6.02 (1H, d, J=3.5Hz); 5.7 (1H, d, J=3.5Hz); 7.6 (2H, d, J=8.5Hz); 7.94 (2H, d, J=8.5Hz) 34 —CH₃ H H

Mol. Wt. = 313 Yield = 89% ¹H: 1.03-1.69 (11H, m); 2.3 (3H, s); 3.6 (2H, t, J=6.0Hz); 3.7 (2H, d, J=6.2Hz); 4.04 (2H, t, J=6Hz); 5.9 (1H, d, J=3.3Hz); 6.0 (1H, d, J=3.3Hz); 6.88 (2H, d, J=8.5Hz); 7.29 (2H, d, J=8.5Hz) 35 —CH₃ H H

Mol. Wt. = 207 Yield = 55% ¹H: 2.3 (3H, s); 3.74 (2H, t, J=3.4Hz); 4.13 (2H, t, J=6Hz); 5.9 (1H, d, J=3.4Hz); 6.2 (1H, d, J=3.4Hz); 7.03-7.05 (2H, m); 7.25-7.27 (1H, m) 36 —CH₃ H H

Mol. Wt. = 307 Yield = 98% ¹H: 2.3 (3H, s); 3.58 (2H, t, J=6.0Hz); 4.0 (2H, t, S=6.0Hz); 5.0 (2H, s); 5.91 (1H, d, J=3.3Hz); 6.0 (1H, d, J=3.3Hz); 6.96-6.99 (2H, m); 7.27-7.45 (7H, m) 37 H H H

Mol. Wt. = 187 Yield = 99% ¹H: 3.7 (2H, t, J=5.4Hz); 4.1 (2H, t, J=5.4Hz); 6.23 (2H, m); 6.8 (1H, m); 7.4-7.8 (5H, m) 38 —CH₃ H H

Mol. Wt. = 165 Yield = 61% ¹H: 0.58-0.61 (2H, m); 0.79-0.85 (2H, m); 1.66-1.7 (1H, m); 2.24 (3H, s); 3.87 (2H, t, J=5.87) Hz; 4.11 (2H, t, J=5.89Hz); 5.69 (1H, d, J=3.26Hz); 5.76 (1H, d, J=3.2Hz) 39 —CH₃ H H

Mol. Wt. = 241 Yield = 47% ¹H: 2.36 (3H, s); 3.93 (2H, t, J=5.77Hz); 4.32 (2H, t, J=5.76Hz); 6.0 (1H, d, J=3.63Hz); 6.57 (1H, d, J=3.63Hz); 6.69 (1H, s); 7.54-7.2 (4H, m) 40 —CH₃ COOCH₃ H

Mol. Wt. = 259 Yield = 92% ¹H: 2.63 (3H, s); 3.61-3.63; (2H, m); 3.79 (3H, s); 4.07-4.15 (2H, m); 6.54 (1H, s); 7.34-7.43 (5H, m) 41 —CH₃ H H

Mol. Wt. = 241 Yield = 58% ¹H: 2.3 (3H, s); 3.74 (2H, t, J=5.7Hz); 4.13 (2H, t, J=5.9Hz); 5.9 (1H, d, J=3.0Hz); 6.1 (1H, d, J=3.5Hz); 6.8 (1H, d, J=3.8Hz); 6.84 (1H, d, J=3.8Hz) 42 —CH₃ H H

Mol. Wt. = 245 Yield = 99% ¹H: 1.43 (3H, t, J=6.97Hz); 2.33 (3H, s); 3.6 (2H, t, J=5.99Hz); 4.02 (4H, m); 5.94 (1H, d, J=3.28Hz); 6.04 (1H, d, J=3.35Hz); 6.91 (2H, d, J=8.69Hz); 7.28 (2H, d, J=8.6.9Hz) 43 —CH₃ H H

Mol. Wt. = 221 Yield = 93% ¹H: 2.3 (3H, s); 2.4 (3H, s); 3.74 (2H, t, J=6.0) Hz; 4.13 (2H, t, J=6Hz); 5.9 (1H, d, J=3.4Hz), 6.17 (1H, d, J=3.4Hz); 6.67 (1H, d, J=3.4Hz); 6.8 (1H, d, J=3.4Hz); 44 —CH₃ CH₃ H C₆H₅ Mol. Wt. = 215 Yield = 50% ¹H: 2.06 (3H, s); 2.2 (3H, s); 3.62 (2H, t, J=6Hz); 4.07 (2H, t, J=6Hz); 6.0 (1H, s); 7.25 (1H, m); 7.3-7.4 (4H, m) 45 —CH₃ H H

Mol. Wt. = 245 Yield = 100% ¹H: 2.32 (3H, s); 3.62 (2H, t, J=6.03Hz); 4.05 (2H, t, J=6.04Hz); 5.92 (1H, d, J=3.27Hz); 5.98 (2H, s); 6.03 (1H, d, J=3.36Hz); 6.84 (2H, d, J=6Hz); 7.16 (1H, s) 46 —CH₃ H H

Mol. Wt. = 251 Yield = 36% ¹H: 2.37 (3H, s); 3.42 (2H, t, J=5.85Hz); 3.5-3.8 (2H, m); 6.02 (1H, d, J=3.27Hz); 6.15 (1H, d, J=3.36Hz); 7.43-7.89 (7H, m) 47 —CH₃ H H

Mol. Wt. = 307 Yield = 100% ¹H: 2.31 (3H, s); 3.56 (2H, t, J=6.03Hz); 4.03 (2H, t, J=6.03Hz); 5.08 (2H, s); 5.94 (1H, d, J=3.36Hz); 6.1 (1H, d, J=3.39Hz); 6.93-7.44 (9H, m) 48 —CH₃ H H

Mol. Wt. = 286 Yield = 30% ¹H: 2.31 (3H, s); 3.76 (2H, t, J=5.9Hz); 4.1 (2H, t, J=5.9Hz); 5.9 (1H, d, J=3.48Hz); 6.95 (1H, d, J=3.54Hz); 6.7 (1H, d, J=3.78Hz); 6.9 (1H, d, J=3.78Hz). 49 —CH₃ H H

Mol. Wt. = 259 Yield = 100% ¹H: 1.33 (6H, d, J=5.13Hz); 2.94 (3H, s); 3.60 (2H, t, J=6.07Hz); 4.03 (2H, t, J=6.07Hz); 4.52-4.60 (1H, m); 5.92 (1H, d, J=2.82Hz); 6.03 (1H, d, J=3.36Hz); 6.88 (2H, d, J=8.7Hz); 7.27 (2H, d, J=8.67Hz) 50 —CH₃ H CH₃

Mol. Wt. = 215 Yield = 57% ¹H: 1.97 (3H, s); 2.29 (3H, s); 3.51 (2H, t, J=6Hz); 3.95 (2H, t, J=6Hz); 5.83 (1H, s); 7.25-7.43 (5H, m)

PREPARATION 2 1-(2-hydroxyethyl)-2-ethyl-1H-pyrrole (compound no. 51)

A mixture containing 1-(2-bromoethyl)-2-acetyl-1H-pyrrole (8.2 g), ethylene glycol (45 mL), 85% potassium hydroxide pellets (8.91 g) and 80% hydrazine hydrate (6.76 mL) was stirred at 200° C. for about 1.5 hr along simultaneous distillation of volatile materials. The product obtained was extracted with ethyl acetate (2×100 mL). The ethyl acetate layer was washed with water (100 mL), dried over sodium sulfate, filtered and evaporated. The crude product obtained was purified by column chromatography (silica gel 100-200), using ethyl acetate:pet. ether (8:2) as an eluent to obtain 2.2 g of the title compound.

TABLE 2 Substituents on the Comp. pyrrole ring in (1e) No. R¹ R² R³ R⁴ 51. C₂H₅ H H H Mol. Wt. = Yield = 139 42% ¹H: 1.26(3H, t, J=6.0Hz); 2.59(2H, q, J₁=7.62Hz, J₂=7.44Hz); 3.84(2H, t, J=5.4Hz); 3.98(2H, t, J=5.35Hz); 5.92-5.93(1H, m); 6.11(1H, t, J=3.12Hz); 6.65(1H, t, J=2.22Hz).

PREPARATION 3 1-(2-Bromoethyl)-1H-pyrrole-2-carbaldehyde (compound no. 52)

A mixture of 2-formylpyrrole (1 g), potassium hydroxide (2.3 g) and dry, DMSO (20 mL) was stirred under nitrogen atmosphere. 1,2-dibromoethane (7.9 g) was added dropwise at 20-25° C. and stirred till the reaction is complete. Water (50 mL) was added and the reaction mixture was extracted with diethyl ether (3×50 mL). The combined organic layer washed with water (30 mL) followed by brine (30 mL) and vas dried over Na₂SO₄. The solvent was evaporated and the compound obtained vas purified by column chromatography (silica gel 100-200) using ethyl acetate:hexane (2:8) as an eluent to obtain the title compound.

In like manner to that described in Preparation 3, following compounds of the formula (1c) (Given in Table 3) were prepared from the appropriately substituted pyrrole derivatives. The latter can be synthesized by using various routes found in literature.

TABLE 3 (1c)

Substituents on the Comp. pyrrole ring in (1c) No. R¹ R² R³ R⁴ 52. CHO H H H Mol. Wt. = 202 Yield = 47% ¹H: 3.65 (2H, t, J=6Hz); 4.65 (2H, t, J=6Hz); 6.33 (1H, m); 6.95-7.05 (2H, m); 9.5 (1H, m). 53. COCH₃ H H H Mol. Wt. = 216 Yield = 32% ¹H: 2.44 (3H, s); 3.67 (2H, t, J=6Hz); 4.65 (2H, t, J=6Hz); 6.16-6.18 (1H, m); 6.94 (1H, t, J=6Hz); 7.01-7.03 (1H, m). 54. —COPh H H H Mol. Wt. = 277 Yield = 66% ¹H: 3.79 (2H, t, J=6.08Hz): 4.75 (2H, t, J=6.12Hz); 6.22 (1H, dd, J₁=2.57Hz, J₂=2.53Hz); 6.825 (1H, dd, J₁=1.64Hz, J₂=1.67Hz); 7.06-7.08 (1H, m); 7.45-7.80 (5H, 1m)

PREPARATION 4 Preparation of 1 (2-hydroxyethyl)-2-methylthio-1H-pyrrole (compound no. 55)

To a mixture of potassium hydroxide (7.9 g) and dry DMSO (90 mL), 2-thiomethylpyrrole (4 g) was added dropwise at 20-25° C., with stirring wider nitrogen atmosphere Stirring was continued for 1 hr at 20-25° C. Ethyl bromoacetate (11.85 g) was added dropwise at 20-25° C. and stirring was continued for 2 hr. In the reaction mixture (100 mL) DM water was added and pH was made acidic (pH=3) with 20% HCl (30 mL). The reaction mixture was extracted with diethyl ether (2×50 mL). The combined organic as extract was washed with DM water (50 mL), saturated brine (50 mL) and dried over Na₂SO₄. The solvent was evaporated to obtain 2-thiomethylpyrrol-1-yl-acetic acid (4.5 g).

To a suspension of sodium borohydride (1.77 g) in tetrahydrofuran (50 mL), thiomethylpyrrol-1-yl-acetic acid (4 g) dissolved in THF (50 mL) was added dropwise at 20° C.-25° C. within 10-15 min under nitrogen atmosphere. When the evolution of hydrogen gas ceases the reaction mixture was cooled to 5-10° C. and iodine (5.94 g) dissolved in THF (20 mL) was added dropwise at 5° C.-10° C. and was stirred further for 2 hrs at 20° C.-25° C. The reaction mixture poured in mixture of ice-cold KOH solution (10 mL) and DM water (50 mL). The solution was extracted with ethyl acetate (2×50 mL). The organic extract washed with water (30 mL), brine (30 mL) and dried over Na₂SO₄. The solvent was evaporated under reduced pressure, to obtain the title compound.

In like manner to that described in Preparation 4, following compounds of the formula (1e) (Given in Table 4) were prepared from the appropriately substituted pyrrole. The latter can be synthesized by using various routes found in literature.

TABLE 4 (1e)

Comp. Substituents on the pyrrole ring in (1e) No. R¹ R² R³ R⁴ 55. SCH₃ H H H Mol. Wt. = 157 Yield = 90% ¹H: 2.2 (3H, s); 3.85 (2H, t, J=6.0Hz); 4.1 (2H, t, J=5.5Hz); 6.14 (1H, dd); 6.38 (1H, dd); 6.85 (1H, dd) 56.

H CH₃ H Mol. Wt. = 201 Yield = 13% ¹H: 2.05 (3H, s); 3.75 (2H, t, J=6Hz); 4.03 (2H, t, J=5.5Hz); 6.07 (1H, s); 6.62 (1H, s); 7.27-7.42 (5H, m). 57. CH₃ H

H Mol. Wt. = 201 Yield = 57% ¹H: 2.24 (3H, s); 3.82-4.01 (4H, m); 6.19 (1H, s); 6.9 (1H, s); 7.1-7.4 (5H, m). 58. CH₃ H CH₃ H Mol. Wt. = 139 Yield = 40.4% ¹H: 2.02 (3H, s); 2.19 (3H, s); 3.7-3.9 (4H, m); 5.73 (1H, s); 6.38 (1H, s).

PREPARATION 5 Preparation of Methyl 2-(5-ethyl-2-phenyl-1H-pyrrol-1-yl)ethane sulfonate (Compound No. 80)

To a solution of compound 17 (4.0, in, 30 mL dichloromethane) obtained in preparation 1, triethylamine (2.75 mL) was added followed by addition of methanesulfonyl chloride (2.1 g) at 0° C. The reaction mixture was stirred at 0° C. for 1h under nitrogen atmosphere. The mixture was warmed to temperature of about 20 to 25° C. and was stirred at that temperature for about 2 h (TLC). After the completion of the reaction, water (30 mL) was added and the organic layer was separated. The mixture was washed with saturated sodium bicarbonate solution (20 mL), water (20 mL) and then with brine (20 mL) and dried over Na₂SO₄. The organic layer was concentrated under reduced pressure. The crude substance was used in the next step without purification.

In like manner to that described in Preparation 5 following compounds of the formula (1c) (given in Table 5) were prepared from the appropriately substituted pyrrole derivatives (1e) described earlier.

TABLE 5 Comp. Substituents on the pyrrole ring in (1c) No. R¹ R² R³ R⁴ 59. CH₃ H CH₃ H Mol. Wt. = 217 Yield = 98% — 60. C₂H₅ H H H Mol. Wt. = 217 Yield = 90% ¹H: 1.29 (3H, t, J=2.64Hz); 2.58 (2H, q, J=7.32Hz); 2.71 (3H, s); 4.15 (2H, t, J=5.52Hz); 4.41 (2H, t, J=5.5Hz); 5.92 (1H, m); 6.11 (1H, t, J=3.16Hz); 6.63 (1H, t, J=2.26Hz). 61. CH₃ H H CH₂CH₃ Mol. Wt. = 231 Yield = 56% ¹H: 1.26 (3H, t, J=7.4Hz); 2.25 (3H, m) 2.57 (2H, q, J=7.42Hz); 2.69 (3H, s); 4.12 (2H, t, J=5.9Hz); 4.34 (2H, t, J=5.9Hz); 5.8-5.83 (2H, m). 62. CH₃ H H (CH₂)₂CH₃ Mol. Wt. = 246 Yield = 45% ¹H: 1.02 (3H, J=7Hz); 1.65 (2H, m); 2.25 (3H, s); 2.5 (2H, t, J=7.7Hz); 2.69 (3H, s); 4.1 (2H, t, J=5.9Hz); 4.35 (2H, t, J=5.9Hz); 5.8-5.83 (2H, m) 63. CH₃ H H (CH₂)₃CH₃ Mol Wt. = 259 Yield = 72% ¹H: 0.95 (3H, t, J=7.2Hz); 1.44-1.46 (2H, m); 1.58-1.62 (2H, m); 2.25 (3H, s); 2.5 (2H, t, J=5.9Hz); 2.7 (3H, s); 4.1 (2H, t, J=5.9Hz); 4.39 (2H, t, J=5.9Hz); 5.8 (2H, s). 64. CH₃ H H

Mol. Wt. = 279 Yield = 98% ¹H: 2.34 (3H, s); 2.83 (3H, s); 4.11 (2H, t, J=5.7Hz); 4.27 (2H, t, J=5.7Hz); 5.96 (1H, d, J=3.4Hz); 6.10 (1H, d, J=3.4Hz); 7.27-7.43 (5H, m). 65. CH₃ H

H Mol. Wt. = 279 Yield = 86% ¹H: 2.28 (3H, s); 2.73 (3H, m); 4.16 (2H, d, J=5.4Hz); 4.4 (2H, d, J=5.4Hz); 6.2 (1H, s); 6.9 (1H, s); 7.17 (1H, d, J=6.75Hz); 7.3 (2H, d, J=7.0Hz); 7.46 (2H, d, J=7.0Hz). 66. CH₃ H H

Mol. Wt. = 293 Yield = 68% ¹H: 2.33 (3H, s); 2.38 (3H, s); 2.65 (3H, s); 4.12 (2H, t, J=6.3Hz); 4.25 (2H, t, J=6.3Hz); 5.95 (1H, d, J=3.4Hz); 6.10 (1H, d, J=3.4Hz); 7.19-7.25 (4H, m). 67. CH₃ H H

Mol. Wt. = 293 Yield = 95% ¹H: 2.33 (3H, s); 2.38 (3H, s); 2.66 (3H, s); 4.12 (2H, t, J=5.8Hz); 4.27 (2H, t, J=5.7Hz); 5.95 (1H, d, J=3.37Hz); 6.09 (1H, d, J=3.42Hz); 7.12-7.16 (2H, m); 7.25-7.31 (2H, m). 68. CH₃ H H

Mol. Wt. = 293 Yield = 55% ¹H: 2.34 (3H, s); 2.38 (3H, s); 2.67 (3H, s); 4.13 (2H, t, J=5.8Hz); 4.27 (2H, t, J=5.7Hz); 5.96 (1H, d, J=3.36Hz); 6.1 (1H, d, J=3.39Hz); 7.13-7.29 (4H m). 69. CH₃ H H

Mol. Wt. = 309 Yield = 62% ¹H: 2.3 (3H, s); 2.67 (3H, s); 3.8 (3H, s); 4.12 (2H, t, J=5.45Hz); 4.24 (2H, t, J=5.45Hz); 5.9 (1H, d, J=3.39Hz); 6.0 (1H, d, J=3.39Hz); 6.95 (2H, d, J=6.78Hz); 7.26 (2H, d, J=6.78Hz). 70. CH₃ H H

Mol. Wt. = 358 Yield = 70% ¹H: 2.33 (3H, s); 2.7 (3H, s); 4.13-4.15 (2H, m); 4.2-4.25 (2H, m); 5.97 (1H, d, J=3.4Hz); 6.12 (1H, d, J=3.4Hz); 7.21-7.26 (2H, m); 7.52-7.55 (2H, m). 71. CH₃ H H

Mol. Wt. = 297 Yield = 90% ¹H: 2.3 (3H, s); 2.7 (3H, s); 3.6 (2H, t, J=6.0Hz); 4.1 (2H, d, J=5.6Hz); 4.22 (2H, d, J=3.4Hz); 5.9 (1H, d, J=3.4Hz); 6.0 (1H, d, J=3.4Hz); 7.04-7.1 (2H, m); 7.2-7.3 (2H, m). 72. CH₃ H H

Mol. Wt. = 313.5 Yield = 82% ¹H: 2.3 (3H, s); 2.69 (3H, s); 4.15 (2H, d, J=6.3Hz); 4.25 (2H, d, J=6.3Hz); 5.96-5.97 (1H, dd); 6.1 (1H, d, J=3.4Hz); 7.27-7.4 (4H, m). 73.

H CH₃ H Mol. Wt. = 279 Yield = 90% ¹H: 2.13 (3H, s); 2.73 (3H, m); 4.2-4.28 (4H, m); 6.05 (1H, s); 6.59 (1H, s); 7.29-7.43 (5H, m). 74. CH₃ H

Mol. Wt. = 355 Yield = 90% ¹H: 2.3 (3H, s); 2.73 (3H, s); 4.09-4.14 (4H, m); 6.2 (1H, s); 7.0-7.4 (10H, m). 75. i-Pr H H i-Pr Mol. Wt. = 272 Yield = 37% ¹H: 1.23-1.25 (12H, d, J=6.7Hz); 2.76 (3H, s); 2.82-2.99 (2H, m); 4.18 (2H, m); 4.33 (2H, m); 5.86 (2H, s) 76. i-Pr H H

Mol. Wt. = 307 Yield = 100% ¹H: 1.30 (6H, t, J=6.78Hz); 2.65 (3H, m); 2.96-3.00 (1H, m); 4.04 (2H, t, J=6Hz); 4.32 (2H, t, J=6Hz); 6.0 (1H, d, J=3.54Hz); 6.12 (1H, d, J=3.54Hz); 7.32-7.43 (5H, m). 77. i-Pr

H

Mol. Wt. = 444 Yield = 15% ¹H: 1.5-1.52 (6H, d, J=7.1Hz); 2.84 (3H, s); 3.44-3.52 (1H, m); 4.12-4.15 (2H, t, J=6.4Hz); 4.3-4.34 (2H, t, J=6.4Hz); 6.32 (1H, s); 7.12-7.18 (3H, t, J=8.5Hz); 7.3-7.4 (4H, m); 7.56-7.59 (2H, d, J=7.6Hz). 78. SCH₃ H H H Mol. Wt. = 235 Yield = 95% ¹H: 2.29 (3H, s); 2.77 (3H, s); 4.35-4.48 (4H, m); 6.17 (1H, dd); 6.4 (1H, dd); 6.85 (1H, dd). 79. C₂H₅ H H C₂H₅ Mol. Wt. = 245 Yield = 82% ¹H: 1.27 (6H, t, 7.3Hz); 2.58 (4H, q, J=7.4Hz); 2.7 (3H, s); 4.11 (2H, t, J=6.04Hz); 4.34 (2H, t, J=6.2Hz); 5.8 (2H, s) 80. C₂H₅ H H

Mol. Wt. = 293 Yield = 92% ¹H: 1.33 (3H, t, J=7.3Hz); 2.6-2.7 (5H, m); 4.1 (2H, t, J=5.9Hz); 4.28 (2H, t, J=5.9Hz); 5.9 (1H, d, J=3.59Hz); 6.1 (1H, d, J=3.48Hz); 7.3-7.43 (5H, m) 81. CH₃ H H

Mol. Wt. = 307 Yield = 96% ¹H: 2.24 (3H, s); 2.65 (3H, s); 2.8-2.85 (2H, m); 2.94-2.99 (2H, m); 4.03 (2H, t, J=5.8Hz); 4.28 (2H, t, J=5.8Hz); 5.84 (1H, d, J=3.39Hz); 5.9 (1H, d, J=3.39Hz); 7.18-7.23 (3H, m). 7.31-7.32 (2H, m) 82. CH₃ H H

Mol. Wt. = 309 Yield = 75% ¹H: 2.34 (3H, s); 2.68 (3H, s); 3.83 (3H, s); 4.16 (2H, t, J=5.6Hz); 4.29 (2H, t, J=5.9Hz); 5.96 (1H, d, J=3.36Hz); 6.12 (1H, d, J=3.42Hz); 6.94-7.34 (4H, m) 83. CH₃ H H

Mol. Wt. = 285 Yield = 84% ¹H: 1.21-1.88 (10H, m); 2.24 (3H, s) 2.24-2.45 (1H, m); 2,7 (3H, s); 4.12 (2H, t, J=5.94Hz); 4.34 (2H, t, J=6Hz); 5.79-5.83 (2H, m) 84. CH₃ H H

Mol. Wt. = 355 Yield = 74% ¹H: 2.35 (3H, s); 2.68 (3H, s); 4.17 (2H, t, J=5.59Hz); 4.33 (2H, t, J=5.55Hz); 5.99 (1H, d, J=2.49Hz); 6.12 (1H, d, J=3.18Hz); 7.2-7.65 (9H, m) 85. CH₃ H H

Mol. Wt. = 269 Yield = 84% ¹H: 2.31 (3H, s), 2.69 (3H, s); 4.35 (2H, t, J=5.2Hz); 4.43 (2H, J=4.9Hz); 5.91-5.92 (1H, d, J₁=0.68Hz, J₂=0.73Hz); 6.3 (2H, d, J=3.5Hz); 6.35 (1H, d, J=2.8Hz); 7.41-7.42 (1H, dd, J₁=0.7Hz, J₂=0.65Hz) 86. CH₃ H H

Mol. Wt. = 283 Yield = 90% ¹H: 2.30 (3H, s); 2.32 (3H, s); 2.68 (3H, s), 3.88 (2H, t, J=5.2Hz); 4.20 (2H, t, J=4.9Hz); 5.93 (1H, d, J=3.5Hz); 6.33 (1H, d, J=3.5Hz); 6.22 (1H, d, J=3.09Hz); 6.27 (1H, d, J=3.54Hz) 87. CH₃ H H

Mol. Wt. = 325 Yield = 80% ¹H: 2.33 (3H, s); 2.5 (3H, s); 2.68 (3H, s); 4.14 (2H, t, J=5.82Hz); 4.25 (2H, t, J=5.64Hz); 5.96 (1H, d, J=3.33Hz); 6.0 (1H, d, J=3.4Hz); 7.25-7.27 (4H, m) 88. CH₃ H H

Mol. Wt. = 304 Yield = 90% ¹H: 2.36 (3H, s); 2.73 (3H, s); 4.16 (2H, t, J=5.6Hz); 4.32 (2H, t, J=5.8Hz), 6.03 (1H, d, J=3.5Hz); 6.238 (1H, d, J=3.54Hz); 7.45 (2H, d, J=8.5Hz); 7.69 (2H, d, J=8.5Hz) 89. CH₃ H H

Mol. Wt. = 371 Yield = 85% ¹H: 2.33 (3H, s); 2.69 (3H, s); 4.15 (2H, t, J=5.5Hz); 4.26 (2H, t, J=5.7Hz); 5.96 (1H, d, J=3.29Hz); 6.09 (1H, d, J=3.4Hz); 7.0-7.39 (9H, m) 90. CH₃ H H

Mol. Wt. = 422 Yield = 93% ¹H: 2.3 (3H, s); 2.4 (3H, s); 2.75 (3H, s); 3.96 (2H, t, J=5.8Hz); 4.18 (2H, t, J=5.98Hz); 5.68 (1H, d, J=3.47Hz); 5.86 (1H, d, J=3.38Hz); 6.27-6.28 (1H, dd, J₁=1.72Hz, J₂=1.75Hz); 6.32 (1H, t, J=3.3Hz); 7.18 (2H, d, J=8.3Hz); 7.41 (2H, d, J=8.3Hz); 7.46-7.47 (1H, dd, J₁=1.7Hz, J₂=1.72Hz) 91. CH₃ H H

Mol. Wt. = 339 Yield = 78% ¹H: 2.26 (3H, s); 2.7 (3H, s); 3.89 (3H, s); 3.92 (3H, s); 4.15-4.25 (4H, m); 5.95 (1H, d, J=3.0Hz); 6.0 (1H, d, J=3.1Hz); 6.87-7.26 (3H, m) 92. CH₃ H H

Mol. Wt. = 336 Yield = 90% ¹H: 2.1 (3H, s); 2.29 (3H, s); 2.69 (3H, s); 4.11 (2H, t, J=5.35Hz); 4.27 (2H, t, J=5.6Hz); 7.29 (2H, d, J=8.5Hz); 7.58 (2H, d, J=8.5Hz)(no peak of py proton) 93. CH₃ H H

Mol. Wt. = 406 Yield = 93% ¹H: 1.45-1.65 (6H, m); 2.32 (3H, s); 2.51-2.52 (4H, m); 2.67 (3H, s); 2.8 (2H, t, J=6Hz); 4.1-4.15 (4H, m); 4.2 (2H, t, J=5.5Hz); 5.9 (1H, d, J=3.33Hz); 6.0 (1H, d, J=3.4Hz); 6.96 (2H, d, J=8.5Hz); 7.26 (2H, d, J=8.5Hz) 94. CH₃ H H

Mol. Wt. = 335 Yield = 73% ¹H: 2.32 (3H, s); 2.67 (3H, s); 4.14 (2H, t, J=5.3Hz); 4.23 (2H, t, J=5.5Hz); 4.57 (2H, d, J=5.3Hz) Hz; 5.32-5.47 (1H, dd, J₁=1.35Hz, J₂=1.35Hz); 5.4-5.48 (1H, dd, J=1.5Hz, 1.5Hz); 5.9 (1H, d, J=3.36Hz); 6.05 (1H, d, J=3.42Hz); 6.08-6.14 (1H, m); 6.94 (2H, d, J=8.5Hz); 6.728 (2H, d, J=8.5Hz) 95. CH₃ H H

Mol. Wt. = 357 Yield = 93% ¹H: 2.36 (3H, s); 2.74 (3H, s); 3.1 (3H, s); 4.15 (2H, t, J=5.86Hz); 4.34 (2H, t, J=5.83Hz); 6.03 (1H, d, J=3.5Hz); 6.25 (1H, d, J=3.54Hz); 7.5 (2H, d, J=8.5Hz); 7.97 (2H, d, J=8.5Hz) 96. CH₃ H H

Mol. Wt. = 391 Yield = 90% ¹H: 1.03-1.69 (11H, m); 2.3 (3H, s); 2.67 (3H, s); 3.7 (3H, t, J=6.24Hz); 4.11 (2H, t, J=3.3Hz); 4.2 (2H, t, J=3.3Hz); 5.9 (1H, d, J=3.39Hz); 6.04 (1H, d, J=3.39Hz); 6.91 (2H, d, J=8.5Hz); 7.24 (2H, d, J=8.5Hz) 97. CH₃ H H

Mol. Wt. = 285 Yield = 94% ¹H: 2.3 (3H, s); 2.6 (3H, s); 4.29 (4H, m); 5.9 (1H, d, J=3.4Hz); 6.2 (1H, d, J=3.4Hz); 6.9-7.01 (1H, m); 7.05-7.06 (1H, m); 7.29 (1H, m) 98. CH₃ H H

Mol. Wt. = 385 ¹H: 2.3 (3H, s); 2.7 (3H, s); 4.13 (2H, t, J=5.3Hz); 4.2 (2H, t, J=5.3Hz); 5.09 (2H, s); 5.9 (1H, d, J=3.3Hz); 6.0 (1H, d, J=3.3Hz); 7.0 (2H, d, J=8.7Hz); 7.25-7.46; (7H, m) 99. H H H C₆H₅ Mol. Wt. = 265 Yield = 40% ¹H: 2.7 (3H, s); 4.12 (4H, m); 6.22 (2H, m); 6.8 (1H, m); 7.3-7.9 (5H, m) 100. CH₃ H H

Mol. Wt. = 320 Yield = 98% ¹H: 2.3 (3H, s); 2.75 (3H, s); 4.29 (4H, m); 5.9 (1H, d, J=3.4Hz); 6.2 (1H, d, J=3.5Hz); 6.78 (1H, d, J=3.78Hz); 6.88 (1H, d, J=3.4Hz) 101. CH₃ H H

Mol. Wt. = 323 Yield = 99% ¹H: 1.44 (3H, t, J=6.98Hz); 2.33 (3H, s); 2.67 (3H, s); 4.05 (2H, t, J=6.98Hz); 4.09 (2H, t, J=5.0Hz); 4.23 (2H, m), 5.94 (1H, d, J=3.24Hz); 6.04 (1H, d, J=3.34Hz); 6.93 (2H, d, J=9.43Hz); 7.26 (2H, d, J=8.63Hz) 102. CH₃ H H

Mol. Wt. = 299 Yield = 96% ¹H: 2.3 (3H, s); 2.6 (3H, s); 4.29 (4H, s); 5.9 (1H, d, J=3.4Hz); 6.17 (1H, d, J=3.5Hz); 6.7 (1H, d, J=3.4Hz); 6.77 (1H, d, J=3.4Hz) 103. CH₃ CH₃ H C₆H₅ Mol. Wt. = 293 Yield = 92% ¹H: 2.04 (3H, s); 2.24 (3H, s); 2.67 (3H, s); 4.12 (2H, t, J=5.6Hz); 4.24 (2H, t, J=5.6Hz); 6.01 (1H, s); 7.2-7.4 (5H, m) 104. CH₃ H H

Mol. Wt. = 243 Yield = 95% ¹H: 0.59-0.62 (2H, m); 0.82-0.87 (2H, m); 1.5-1.6 (1H, m); 2.24 (3H, s); 2.69 (3H, s); 4.27 (2H, t, J=5.9Hz); 4.45 (2H, t, J=5.8Hz), 5.68 (1H, d, J=3.3Hz); 5.75 (1H, d, J=3.34Hz) 105. CH₃ H H

Mol. Wt. = 319 Yield = 81% ¹H: 2.36 (3H, s); 2.73 (3H, s); 3.93 (2H, t, J=5.77Hz); 4.32 (2H, t, J=5.76Hz); 6.0 (1H, d, J=3.63Hz); 6.57 (1H, d, J=3.63Hz); 6.69 (1H, s); 7.54-7.72 (4H, m) 106. CH₃ COOCH₃ H

Mol. Wt. = 337 Yield = 84% ¹H: 2.64 (3H, s); 2.73 (3H, s); 3.81 (3H, s); 4.11 (2H, t, J=5.76Hz): 4.29 (2H, t, J=5.76Hz); 6.56 (1H, s); 7.26-7.45 (5H, m). 107. CH₃ H H

Mol. Wt. = 323 Yield = 85% ¹H: 2.32 (3H, s); 2.7 (3H, s); 4.14 (2H, t, J=5.37Hz), 4.23 (2H, t, J=5.47Hz); 5.92 (1H, d, J=2.85Hz); 6.0 (2H, s); 6.03 (1H, d, J=3.39Hz); 6.74-6.86 (3H, m) 108. CH₃ H H

Mol. Wt. = 329 Yield = 97% ¹H: 2.39 (3H, s); 2.59 (3H, s); 3.91-3.98 (2H, m); 4.1-4.16 (2H, m); 6.07 (1H, d, J=3.33Hz); 6.17 (1H, d, J=3.36Hz); 7.43-7.90 (7H, m) 109. CH₃ H H

Mol. Wt. = 385 Yield = 100% ¹H: 2.31 (3H, s); 2.62 (3H, s); 4.06 (2H, t, J=5.56Hz); 4.18 (2H, t, J=5.65Hz); 5.1 (2H, s); 5.94 (1H, d, J=3.03Hz); 6.1 (1H, d, J=3.42Hz); 6.92-7.44 (9H, m) 110. CH₃ H H

Mol. Wt. = 364 Yield = 96% ¹H: 2.32 (3H, s); 2.73 (3H, s); 4.28 (4H, s); 5.9 (1H, d, J=3.5Hz); 6.2 (1H, d, J=3.54Hz); 6.7 (1H, d, J=3.75Hz); 7.02 (1H, d, J=3.81Hz) 111. CH₃ H H

Mol. Wt. = 337 Yield = 100% ¹H: 1.36 (6H, d, J=6.03Hz); 2.32 (3H, s); 2.66 (3H, s); 4.13 (2H, t, J=5.29Hz); 4.22 (2H, t, J=5.53Hz); 4.53-4.61 (1H, m); 5.92 (1H, d, J=3.36Hz); 6.03 (1H, d, J=3.39Hz); 6.90 (2H, d, J=8.7Hz); 7.24 (2H, d, J=8.1Hz) 112. CH₃ H CH₃

Mol. Wt. = 293 Yield = 95% ¹H: 1.88 (3H, s); 2.29 (3H, s); 2.68 (3H, s); 4.03 (2H, t, J=5.26Hz); 4.13 (2H, t, J=5.61Hz); 5.83 (1H, s); 7.26-7.45 (5H, m)

PREPARATION 6 4-[2-(5-Methyl-2-phenylpyrrol-1-yl)ethoxy]benzaldehyde (compound No. 113)

To a suspension of potassium carbonate (16.43 g) in dimethyl formamide (50 mL), 4-hydroxy benzaldehyde (4.37 g) was added and warmed to 90-C to 95° C. To the solution, methyl 1-[5-methyl-2-phenyl-1H-pyrrol-1yl]ethane sulfonate (10 g) (compound no. 64 dissolved in dimethyl formamide (50 mL) w added within 30 min and the reaction was continued for further 4 hours. The reaction mixture was diluted with water (100 mL) and was extracted with ethyl acetate (3×100 mL), washed with water (3×100 mL), brine (200 mL), and was dried over sodium sulfate. The solvent was evaporated under reduced pressure, to yield the title compound.

TABLE 6 (1h)

Substituents on the Comp. pyrrole ring in (1p) No. R¹ R² R³ R⁴ 113. CH₃ H H Phenyl Mol. Wt. = 306 Yield = 99% ¹H: 2.39 (3H, s); 4.0 (2H, t J=6.3Hz); 4.35 (2H, t, J=6.3Hz): 5.98 (1H, d, J=3.4Hz); 6.12 (1H, t, J=3.4Hz); 6.74 (2H, d, J=8.7); 7.38-7.42 (5H, m); 7.73-7.75 (2H, d, J=8.8Hz); 9.85 (1H, s).

EXAMPLE 7 (S)-Ethyl 3-{4-[2-(2-ethyl-5-methyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate (Example 5)

A mixture of (S)-Ethyl 3-(4-hydroxyphenyl)-2-ethoxypropionate (2.24 g) and dry potassium carbonate (3.7 g) in dimethyl formamide (30 mL) was stirred at 80° C. for 30 min. Compound No. 61 (2.27 g) was added at 40° C. and stirring was continued at 80° C. for 24 h. The reaction mixture was cooled to 20° C.-25° C. and 20 mL water was added. The reaction mixture was extracted with ethyl acetate (2×40 mL), washed with water (2×40 mL), brine (40 mL) and was dried over sodium sulfite. The organic layer was evaporated under reduced pressure to obtain oily product. The crude oily product was chromatographed over silica gel (100-200 mesh) using ethyl acetate:petroleum ether (1:9) as an eluent to afford the title compound as a yellow oil (1.654 g, 45%).

PREPARATION 8 (S)-Ethyl 3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate (Example 3)

A mixture of (S)-ethyl 3-(4-hydroxyphenyl)-2-ethoxypropionate (1.12 g) and dry potassium carbonate (2.37 g) in dimethyl formamide (20 mL) was stirred at 80° C. for 30 min. 1-(2-bromoethyl)₂2-carbaldehyde pyrrole (1.0 g, Compound. No. 52) was added at 40° C. and stirring was continued at 80° C. for 24 h. The reaction mixture was cooled to 20° C.-25° C. and 20 mL water was added. The reaction mixture was extracted with ethyl acetate (2×25 mL), washed with water (2×20 mL), brine (25 mL) and was dried over sodium sulfate. The organic layer was evaporated under reduced pressure to obtain an oily product. The crude oily product was chromatographed over silica gel (100-200 mesh) using ethyl acetate:petroleum ether (1:9) as an eluent to afford title compound as a yellow oil (0.4 g 22%).

PREPARATION 9 (S)-Ethyl 3-{4-[2-(5-ethyl-2-phenyllpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate (Example 24)

A mixture of (S)-ethyl 3-(4-hydroxyphenyl)-2-ethoxypropionate (2.3 g), and dry potassium carbonate (2.6 g) in toluene (15 mL) was heated to reflux for 45 min with continuous removal of water using a Dean-Stark water separation. The mixture was cooled to 50° C. and mesylate compound No. 80 (2.9 g) was added. The reaction mixture was continued to reflux for 24 hrs. Later it was cooled to 20° C.-25° C. and toluene was distilled at reduced pressure. To the residue, DM water (30 mL) was added and the crude product was extracted with ethyl acetate (2×25 mL), washed with water (2×20 mL), brine (25 mL) and was dried over sodium sulfate. The solvent was evaporated under reduced pressure to obtain an oily product. The crude oily product was chromatographed over silica gel using ethyl acetate:petroleum ether (60-80) (1:9) as an eluent to afford the title product as a yellow oil (73%).

In like manner to that described in preparation 7-9, the following compounds of the formula (I) (given in Table 7) were prepared from appropriately substituted pyrrole derivatives described in either Table 5 or obtained front other methods described herein.

TABLE 7 (I)

Ex. Substituents on the pyrrole ring in (I) No. R¹ R² R³ R⁴ 1. CH₃ H CH₃ H Mol. Wt. = 359 Yield = 18% ¹H: 1.15 (3H, t, J=7Hz); 1.26 (3H, t, J=7Hz); 2.04 (3H, s); 2.23 (3H, s); 2.91-2.94 (2H, m); 3.3-3.39 (1H, m); 3.5-3.62 (1H, m); 3.92 (1H, dd, J=6.0Hz); 4.12-4.2 (6H, m); 5.7 (1H, s); 6.4 (1H, s); 6.77 (2H, d, J=8.6Hz); 7.15 (2H, d J=8.6Hz). 2. C₂H₅ H H H Mol. Wt. = 359 Yield = 18% ¹H: 1.15 (3H, t, J=7.02Hz); 1.22 (3H, t, J=5.74Hz); 1.26 (3H, t, J=6.03Hz); 2.62 (2H, q); 2.93 (2H, d, J=5.7Hz); 3.3-3.4 (1H, m); 3.5-3.6 (1H, m); 3.94 (2H, t, J=6.0Hz); 4.12-4.20 (5H, m); 5.91 (1H, m); 6.10 (1H, t, J=3.12Hz); 6.69-6.75 (1H, m); 6.76 (2H, d, J=6.7Hz); 7.13 (2H, d, J=8.61Hz). 3. CHO H H H Mol. Wt. = 359 Yield = 22% ¹H: 1.1 (3H, t, J=6.9Hz); 1.26 (3H, t, J=6.9Hz); 2.94-4.08 (5H, m); 4.08-4.1 (2H, m); 4.22 (2H, t, J=4.9Hz); 4.7 (2H, t, J=4.9Hz); 6.23 (1H, d); 6.7 (2H, d, J=8.5Hz); 6.97 (1H, dd); 7.1 (1H, dd); 7.4 (2H, d, J=8.5Hz); 9.5 (1H, s). 4. COCH₃ H H H Mol. Wt. = 137 Yield = 10% ¹H: 1.15 (3H, t, J=3.48Hz); 1.2 (3H, t, J=5.1Hz); 2.44 (3H, s); 2.93 (2H, dd, J=5.55Hz); 3.0-3.35 (2H, m); 3.94 (2H, t, J=3.58Hz); 4.16 (2H, q, J₁=1.44Hz, J₂=1.41Hz); 4.21 (1H, t, J=5.04Hz); 4.69 (2H, t, J=4.99Hz); 6.14-6.15 (1H, m); 6.75 (2H, d, J=8.37Hz); 6.99-7.01 (2H, m) 7.11 (2H, d, J=8.64Hz). 5. CH₃ H H CH₂CH₃ Mol. Wt. = 373 Yield = 45% ¹H: 1.15 (3H, t, J=7Hz); 1.22(3H, t, J=7Hz); 1.27 (3H, t, J=7Hz); 2.28 (3H, m); 2.63 (2H, q, J=7.4Hz); 2.9-2.96 (2H, m); 3.3-3.6 (2H, m); 3.92-4.19 (7H, m); 5.8-5.83 (2H, m); 6.75 (2H, d, J=6.78Hz); 7.14 (2H, d, J=6.78Hz). 6. CH₃ H H (CH₂)₂CH₃ Mol. Wt. = 389 Yield = 41% ¹H: 1.02 (3H, t, J=6.9Hz); 1.15 (3H, t, J=6.9Hz); 1.23 (3H, J=7.14Hz); 1.65-1.7 (2H, m); 2.28 (3H, s); 2.5 (2H, t, J=7.75Hz); 2.9-2.92 (2H, m); 3.25-3.5 (2H, m); 3.94 (1H, t, J=3.66Hz); 4.0-4.2 (6H, m) 5.8-5.83 (2H, m); 6.75 (2H, d, J=8.5Hz); 7.15 (2H, d, J=8.5Hz). 7. CH₃ H H (CH₂)₃CH₃ Mol. Wt. = 401 Yield = 46% ¹H: 0.95 (3H, t, J=7.2Hz); 1.15 (3H, t, J=7Hz); 1.23 (3H, t, J=7Hz); 1.4-1.47 (2H, m); 1.6-1.7 (2H, m); 2.28 (3H, s); 2.5 (2H, t, J=7.7Hz); 2.9-2.97 (2H, m); 3.3-3.39 (1H, m); 3.55-3.63 (1H, m); 4.04-4.22 (7H, m) 5.8-5.83 (2H, m); 6.7 (2H, d, J=8.5Hz); 7.15 (2H, d, J=8.5Hz). 8. CH₃ H H

Mol. Wt. = 421 Yield = 85% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.1Hz); 2.37 (3H, s); 2.9-2.92 (2H, dd); 3.32-3.35 (1H, m) 3.5-3.58 (1H, m); 3.9-3.92 (3H, m); 4.12-4.19 (2H, q); 4.28 (2H, t, J=6.5Hz); 5.96-5.97 (1H, d, J=3.1Hz); 6.1-6.11(1H, d, J=3.11Hz); 6.6 (2H, d, J=8.5Hz); 7.06-7.09 (2H, d, J=8.5Hz); 7.3-7.4 (5H, m). 9. CH₃ H

H Mol. Wt. = 421 Yield = 63% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.1Hz); 2.37 (3H, s); 2.9-2.92 (2H, m); 3.3-3.4 (1H, m); 3.53-3.62 (1H, m); 3.9 (1H, t, J=6.6Hz); 4.1-4.22 (6H, m); 6.2 (1H, s); 6.8 (2H, d, J=8.5Hz); 6.98 (1H, s); 7.15 (2H, d, J=8.5Hz); 7.23-7.33 (3H, m) 7.4 (2H, t, J=7.1Hz). 10. CH₃ H H

Mol. Wt. = 435 Yield = 34% ¹H: 1.16 (3H, t, J=6.9Hz); 1.22 (3H, t, J=6.9Hz); 2.37 (3H, s); 2.39 (3H, s); 2.9-2.92 (2H, m); 3.3-3.37 (1H, m); 3.56-3.62 (1H, m); 3.91-4.2 (5H, m); 4.27 (2H, m); 5.95 (1H, d, J=3.36Hz); 6.10 (1H, d, J=3.36Hz); 6.6 (2H, d, J=8.5Hz); 7.0 (2H, d, J=6.78Hz); 7.19 (2H, d, J=8.5Hz); 7.28 (2H, d, J=6.78Hz). 11. CH₃ H H

Mol. Wt. = 435 Yield = 37% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.13Hz); 2.37 (6H, s); 2.91 (2H, d, J=5.94Hz); 3.89-3.95 (5H, m); 4.15 (2H, q, J₁=7.11Hz, J₂=7.11Hz); 4.28 (2H, t, J=6.63Hz); 5.95 (1H, d, J=3.39Hz); 6.07 (1H, d, J=3.39Hz); 6.59 (2H, d, J=7.62Hz); 7.07 (2H, d, J=8.64Hz); 7.15-7.28 (4H, m). 12. CH₃ H H

Mol. Wt. = 435 Yield = 53% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.3Hz); 2.37 (6H, s); 2.9-2.92 (2H, m); 3.3-3.58 (2H, m); 3.89-3.95 (3H, m); 4.15 (2H, t, 6Hz); 4.28 (2H, t, J=6Hz); 5.95 (1H, d, J=3.2Hz); 6.0 (1H, d, J=3.2Hz); 6.6 (2H, d, J=7.62Hz); 7.0 (2H, d, J=8.64Hz); 7.12-7.28 (4H, m). 13. CH₃ H H

Mol. Wt. = 451 Yield = 41% ¹H: 1.1 (3H, t, J=7Hz): 1.22 (3H, t, J=7Hz); 2.36 (3H, s); 2.9-2.92 (2H, dd); 3.3-3.32 (1H, m); 3.52-3.62 (1H, m); 3.84 (3H, m); 3.9-3.94 (3H, m); 4.14 (2H, t, J=6.68Hz); 4.22 (2H, t, J=6.68Hz); 5.9 (1H, d, J=3.36Hz); 6.0 (1H, d, J=3.36Hz); 6.64 (2H, d, J=8.58Hz); 6.95 (2H, d, J=6.78Hz); 7.10 (2H, d, J=8.5Hz); 7.31 (2H, d, J=6.78Hz). 14. CH₃ H H

Mol. Wt. = 500 Yield = 40% ¹H: 1.15 (3H, t, J=7Hz); 1.2 (3H, t, J=7Hz); 2.37 (3H, s); 2.95 (2H, dd); 3.29-3.38 (1H, m); 3.55-3.63 (1H, m); 3.9-3.95 (3H, m); 4.17 (2H, t, J=6.3Hz); 4.28 (2H, t, J=6.3Hz); 5.9 (1H, d, J=3.42Hz); 6.1 (1H, d, J=3.42Hz); 6.6 (2H, d, J=8.5Hz); 7.21 (2H, d, J=8.5Hz); 7.29 (2H, d, J=8.5Hz); 7.5 (2H, d, J=8.5Hz). 15. CH₃ H H

Mot. Wt. = 439 Yield = 30% ¹H: 1.15 (3H, t, J=6.99Hz); 1.23 (3H, t, J=6.99Hz); 1.58 (3H, s, 2.9-2.93 (2H, dd); 3.32-3.4 (1H, m); 3.55-3.65 (1H, m); 3.85-4.0 (3H, m); 4.1-4.2 (2H, m); 4.24 (2H, t, J=6.4Hz); 5.9 (1H, d, J=3.3); 6.0 (1H, d, J=3.4Hz); 6.6 (2H, t, J=8.6Hz); 7.0-7.1 (4H, m); 7.26-7.38 (2H, m). 16. CH₃ H H

Mol. Wt. = 455.5 Yield = 62% ¹H: 1.15 (3H, t, J=7Hz); 1.23 (3H, t, J=7Hz); 2.36 (3H, s); 2.9-2.95 (2H, dd); 3.33-3.4 (1H, m); 3.53-3.62 (1H, m); 3.9-4.13 (3H, m); 4.18 (2H, t, J=6.3Hz); 4.26 (2H, t, J=6.3Hz); 5.97 (1H, d, J=3.27Hz); 6.1 (1H, d, J=3.4Hz); 6.6 (2H, d, J=8.4Hz); 7.1 (2H, d, J=8.4Hz); 7.25-7.38 (2H, m); 7.4 (2H, d, J=8.5Hz). 17.

H CH₃ H Mol. Wt. = 421 Yield = 13% ¹H: 1.15 (3H, y, J=6.9Hz); 1.23 (3H, t, J=7.2Hz); 2.13 (3H, s); 2.92 (2H, d); 3.33 (1H, m); 3.59 (1H, m); 3.94 (3H, m); 4.07-4.26 (4H, m); 6.05 (1H, s); 6.67-6.72 (3H, m); 7.12 (2H, m); 7.3-7.43 (5H, m). 18. CH₃ H

Mol. Wt. = 497 Yield = 32% ¹H: 1.153 (3H, t, J=7.0Hz); 1.24 (3H, t, J=7Hz); 2.4 (3H, s); 2.9-2.92 (2H, m); 3.33-3.36 (1H, m); 3.53-3.63 (1H, m); 3.85-3.95 (3H, m); 4.1-4.2 (4H, m); 6.2 (1H, s); 6.5-7.4 (14H m). 19. i-Pr H H i-Pr Mol. Wt. = 415 Yield = 36% ¹H: 1.15 (3H, t, J=6.9Hz); 1.23 (3H, t, J=7.0Hz); 1.24-1.26 (12H, d, J=6.7Hz); 2.9 (4H, m); 3.35 1(H); 3.6 (1H, m); 3.95 (1H, m); 4.05 (2H, t); 4.1-4.2 (2H, q, J₁=6.8Hz, J₂=7.1Hz); 4.23 (2H, t, J=6.6Hz); 5.87 (2H, s); 6.75-6.76 (2H, d, J=8.6H); 7.12-7.15 (2H, d, J=8.6Hz) 20. i-Pr H H

Mol. Wt. = 449 Yield = 31% ¹H: 1.14 (3H, t, J=6.99Hz); 1.21 (3H, t, J=5.55 Hz); 1.31 (6H, d, J=6.15Hz); 2.90 (2H, d, J=6.15Hz); 3.1 (1H, m); 3.32-3.57 (2H, m); 3.84 (2H, t, J=6.75Hz); 3.91 (1H, t, J=3.55Hz); 4.12-4.19 (2H, q, J₁=7.14Hz, J₂=7.14Hz); 4.33 (2H, t, J=6.8Hz); 6.00 (1H, d, J=3.51Hz); 6.12 (1H, d, J=3.51Hz); 6.53 (2H, t, J=8.64Hz); 6.93 (2H, d, J=8.7Hz); 7.05 (2H, d, J=8.61Hz); 7.31-7.40 (5H, m). 21. i-Pr

H

Mol. Wt. = 586 Yield = 20% ¹H: 1.15 (3H, t, J=6.9Hz); 1.23 (3H, t, J=7.1Hz); 1.51-1.53 (6H, d, J=7.1Hz); 2.92 (2H, dd, J=7.11Hz); 3.33-3.4 (1H, m); 3.5-3.6 (2H, Complex); 3.9-4.0 (3H, m); 4.1-4.2 (2H, q, J=7.11Hz); 4.3-4.4 (2H, t, J=6.3Hz); 6.31 (1H, s); 6.58-6.61 (2H, d, J=8.5Hz); 7.0-7.2 (4H, m); 7.3-7.4 (4H, m); 7.5 (1H, s); 7.6 (2H, d, J=7.6Hz) 22. SCH₃ H H H Mol. Wt. = 377 Yield = 20% ¹H: 1.14 (3H, t, J=7.0Hz); 1.24 (3H, ,t J=7.0Hz); 2.29 (3H,s); 2.90-2.94 (2H, m); 3.30-3.40 (1H, m); 3.54-3.62 (1H, m); 3.95 (1H, t, J=3.6Hz); 4.13-4.22 (4H, m); 4.40 (2H, t, J=5.6Hz); 6.15 (2H, d, J=3.2Hz); 6.37 (1H, dd); 6.80 (2H, d, J=8.5Hz); 6.94 (1H, m); 7.15 (2H, d, J=8.5Hz). 23. C₂H₅ H H C₂H₅ Mol. Wt. = 387 Yield = 73% ¹H: 1.15 (3H, t, J=7Hz); 1.25 (3H, t, J=7Hz); 1.28 (6H, t, J=7.3Hz); 2.64 (4H, t,J=7.4Hz); 2.92-2.94 (2H, m); 3.29-3.38 (1H, m); 3.53-3.61 (1H, m); 3.94 (1H, t, J=1.38Hz); 4.07 (2H, t, J=5.97Hz); 4.12-4.21 (4H, m); 5.8 (2H, s); 6.7 (2H, d, J=8.6Hz); 7.15 (2H, d, 8.6Hz) 24. C₂H₅ H H C₆H₅ Mol. Wt. = 435 Yield = 73% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.1Hz); 1.24 (3H, t, J=7.3Hz); 2.73 (2H, q, 2=7.4Hz); 2.9-3.1 (2H, m); 3.28-3.38 (1H, m); 3.53-3.61 (1H, m); 3.88-3.95 (3H, m); 4.19 (2H, t, J=7.1Hz); 4.29 (2H, t, J=7.2Hz); 6.0 (1H, d, J=3.42Hz); 6.15 (1H, d, J=3.45Hz); 6.59 (2H, d, J=8.5Hz); 7.0 (2H, d, J=8.5Hz); 7.3-7.4 (5H, m) 25. CH₃ H H

Mol. Wt. = 449 Yield = 72% ¹H: 1.15 (3H, t, J=6.9Hz); 1.25 (3H, t, J=7Hz); 2.29 (3H,,s); 2.9-2.97 (6H, m); 3.29-3.37 (1H, m); 3.53-3.62 (1H, m); 3.9-4.2 (7H, m) 5.85 (1H, d, J=3.1Hz); 5.9 (1H, d, J=3.37Hz); 6.73 (2H, d, J=8.6Hz); 7.13 (2H, J=8.6Hz); 7.21-7.3 (5H, m) 26. CH₃ H H

Mol. Wt. = 497 Yield = 60% ¹H: 1.14 (3H, t, J=6.9Hz); 1.23 (3H, t, J=7.1Hz); 2.39 (3H, s); 2.9 (2H, d, J=6.1Hz); 3.28-3.38 (1H, m); 3.53-3.61 (1H, m); 3.92-4.2 (5H, m); 4.34 (2H, t, J=6.5Hz); 5.9 )1H, d, J=3.3Hz); 6.17 (1H, d, J=3.4Hz); 6.6 (2H, d, J=8.5Hz); 7.0 (2H, d, J=8.5Hz); 7.43-7.5 (5H, m); 7.6-7.68 (4H, m) 27. CH₃ H H

Mol. Wt. = 411 Yield = 60% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7Hz); 2.35 (3H, s); 2.91-2.94 (2H, m); 3.29-3.38 (1H, m); 3.53-3.63 (1H, m); 3.9 (1H, t, J=6.0Hz); 4.12-4.2 (4H, m): 4.4 (2H, t, J=6.4Hz); 5.91-5.92 (1H, m); 6.31-6.38 (2H, m); 6.42-6.45 (1H, m); 6.7 (2H, d, J=8.6Hz); 7.13 (2H, d, J=8.5Hz); 7.41-7.42 (1H, m) 28. CH₃ H H

Mol. Wt. = 467 Yield = 80% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.1Hz); 2.29 (3H, s); 2.3 (3H, s); 2.92 (2H, d, J=7.26Hz); 3.28-3.38 (1H, m); 3.53-3.61 (1H, m); 3.89-3.97 (3H, m); 4.19 (2H, t, J=7Hz); 4.29 (2H, t, J=6.55Hz); 5.96 (1H, d, J=3.36Hz); 6.0 (1H, d, J=3.39Hz); 6.6 (2H, d, J=8.5Hz); 7.0 (2H, d, J=8.5Hz); 7.22-7.33 (4H, m) 29. CH₃ H H

Mol. Wt. = 425 Yield = 60% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.1Hz); 2.29 (3H, s); 2.3 (3H, s); 2.94 (2H, d, J=7.26Hz); 3.3-3.38 (1H, m); 3.54-3.63 (1H, m); 3.94 (1H, t, J=6.0Hz); 4.12-4.19 (4H, m); 4.36 (2H, t, J=6.4Hz); 5.91 (1H, d, J=3.4Hz); 5.9-6.0 (1H, m) 6.22 (1H, d, J=3.06Hz); 6.26 (1H, d, J=3.5Hz); 6.7 (2H, d, J=8.6Hz), 7.13- (2H, d, J=8.58Hz) 30. CH₃ H H

Mol. Wt. = 446 Yield = 70% ¹H: 1.15 (3H, t, J=6.69Hz); 1.23 (3H, t, J=7Hz); 2.38 (3H, s); 2.91-2.95 (2H, m); 3.3-3.40 (1H, m); 3.54-3.64 (1H, m); 3.9-3.98 (3H, m); 4.16 (2H, q, J=7.1Hz); 4.34 (2H, t, J=6.18Hz); 6.0 (1H, d, J=3.48Hz); 6.2 (1H, d, J=3.54Hz); 6.62 (2H, d, J=8.6Hz); 6.75 (2H, d, J=8.49Hz); 7.5 (2H, d, J=8.37Hz); 7.67 (2H, d, J=8.3Hz) 31. CH₃ H H

Mol. Wt. = 513 Yield = 60% ¹H: 1.15 (3H, t, J=7Hz); 1.22 (3H, t, J=6.9Hz); 2.37 (3H, s); 2.93 (2H, d, J=7Hz); 3.29-3.38 (1H, m); 3.54-3.62 (1H, m); 3.94 (3H, t, J=6.2Hz); 4.17 (2H, q, J=7Hz) 4.28 (2H, t, J=6.3Hz); 5.96 (1H, d, J=3.3Hz); 6.08 (1H, d, J=3.39Hz); 6.64 (2H, d, J=8.6Hz); 7.0-7.4 (11H, m) 32. CH₃ H H

Mol. Wt. = 564 Yield = 30% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.1Hz); 2.28 (3H, s); 2.3 (3H, s); 2.95 (2H, d, J=6.5Hz); 3.3-3.38 (1H, m); 3.54-3.62 (1H, m); 3.86-4.2 (7H, m); 5.7 (1H, d, J=3.48Hz); 5.88-7.8 (12H, m) 33. CH₃ H H

Mol. Wt. = 481 Yield = 64% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=9Hz); 2.37 (3H, s); 2.9-2.92 (2H, m); 3.28-3.35 (1H, m); 3.55-3.62 (1H, m); 3.86 (3H, s); 3.91 (3H, s); 3.9-3.95 (3H, m); 4.17 (2H, q, J=7.1Hz); 4.27 (2H, t, J=6.6Hz); 5.96 (1H, d, J=3.39Hz); 6.0 (1H, d, J=3.39Hz); 6.64 (2H, d, J=8.5Hz); 6.91-6.94 (3H, m); 7.1 (2H, d, J=8.5Hz) 34. CH₃ H H

Mol. Wt. = 483 Yield = 90% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=9Hz); 2.38 (3H, s); 2.77 (s, 3H); 2.90-2,93 (2H, m); 3.28-3.38 (1H, m); 3.54-3.62 (1H, m); 3.9-3.99 (3H, m); 4.17 (2H, q, J=7.1Hz); 4.34 (2H, t, J=6.3Hz); 5.9 (1H, d, J=3.48Hz); 6.18 (1H, d, J=3.48Hz); 6.64 (2H, d, J=8.6Hz); 7.11 (2H, d, J=8.6Hz); 7.58 (2H, d, J=8.4Hz); 7.66 (2H, d, J=8.4Hz) 35. CH₃ H H

Mol. Wt. = 464 Yield = 4O% ¹H: 1.15 (3H, t, J=7.0Hz), 1.22 (3H, t, J=6.9Hz); 2.32 (3H, s); 2.8-2.9 (2H, m); 3.23-3.4 (1H, m); 3.48-3.59 (1H, m); 3.64 (3H, s); 3.9 (2H, t, J=6.0Hz); 3.9-4.0 (3H, m); 4.28 (2H, t, J=6.0Hz); 5.85 (1H, d, J=3.28Hz); 5.96 (1H, d, J=3.4Hz); 6.58 (2H, d, J=8.6Hz); 7.02 (2H, d, J=8.5Hz); 7.32 (2H, J=8.5Hz); 7.57 (2H, d, J=8.5Hz) 36. CH₃ H H

Mol. Wt. = 548 Yield = 60% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=6.9Hz); 1.4-1.7 (6H, m); 2.36 (3H, s); 2.5-2.55 (4H, m); 2.79 (2H, t, J=6.06Hz); 2.9-2.95 (2H, m); 3.3-3.41 (1H, m); 3.53-3.62 (1H, m); 3.88-3.98 (3H, m); 4.1-4.2 (4H, m); 4.26 (2H, t, J=6Hz); 5.94 (1H, d, J=3.1Hz); 6.0 (1H, d, J=3.1Hz); 6.6 (2H, d, J=8.5Hz); 6.94 (2H, d, J=8.5Hz); 7.1 (2H, d, J=8.5Hz); 7.31 (2H, d, J=8.6Hz) 37. CH₃ H H

Mol. Wt. = 477 Yield = 50% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.1Hz); 2.36 (3H, s); 2.9 (2H, d, J=7.1Hz); 3.28-3.99 (1H, m); 3.53-3.63 (1H, m); 3.91 (3H, t, J=6.6Hz); 4.15 (2H, q, J=7.1Hz); 4.25 (2H, t, J=6.6Hz); 4.56 (2H, d, J=3.9Hz); 5.29-5.34 (1H, dd); 5.4-5.5 (1H, dd); 5.94 (1H, d, J=2.9Hz); 6.05 (1H, d, J=3.48Hz); 6.08-6.13 (1H, m); 6.63 (2H, d, J=8.6Hz); 6.95 (2H, d, J=8.7Hz,); 7.09 (2H, d, J=8.5Hz); 7.3 (2H, d, J=8.69Hz); 38. CH₃ H H

Mol. Wt. = 529 Yield = 50% ¹H: 1.15 (3H, t, J=7Hz); 1.22 (3H, t, J=7Hz); 2.36 (3H, s); 2.90-2.91 (2H, m); 3.29-3.38 (1H, m); 3.53-3.61 (1H, m); 3.94 (3H, t, J=6.25Hz); 4.19 (2H, q, J=7Hz); 4.3 (2H, t, J=6.3Hz); 5.9 (1H, d, 3.3Hz); 6.11 (1H, J=3.4Hz); 6.6 (2H, d, J=8.67Hz); 7.1 (2H, d, J=8.6Hz); 7.26-1.42 (9H, m) 39. CH₃ H H

Mol. Wt. = 545 Yield = 80% ¹H: 1.15 (3H, t, J=7Hz); 1.22 (3H, t, J=7Hz); 2.36 (3H, s); 2.9-2.93 (2H, m); 3.3-3.39 (1H, m); 3.52-3.64 (1H, m); 3.91-3.94 (3H, m); 4.26 (2H, t, J=6.0Hz); 4.3 (2H, t, J=6.0Hz); 5.97 (1H, d, J=3.6Hz); 6.14 (1H, d, J=3.48Hz); 6.6 (2H, J=8.6Hz); 7.09 (2H, d, J=8.5Hz); 7.46-7.7 (9H, m) 40. CH₃ H H

Mol. Wt. = 499 Yield = 75% ¹H: 1.15 (3H, t, J=7Hz); 1.22 (3H, t, J=7Hz); 2.39 (3H, s); 2.9-3.0 (2H, m); 3.09 (3H, s); 3.4-3.62 (2H, m); 3.91-3.94 (3H, m); 4.26 (2H, t, J=6.0Hz); 4.3 (2H, t, J=6Hz); 6.02 (1H, d, J=3.3Hz); 6.2 (1H, d, J=3.5Hz); 6.6 (2H, d, J=8.58Hz); 7.11 (2H, d, J=8.5Hz); 7.6 (2H, d, J=8.4Hz); 7.9 (2H, d, J=8.4Hz) 41. CH₃ H H

Mol. Wt. = 533 Yield = 64% ¹H: 1.12-1.29 (6H, m); 1.15 (3H, t, J=7Hz); 1.22 (3H, t, J=7Hz); 1.56-1.86 (5H, m); 2.35 (3H, s); 2.9 (2H, d, J=7.05Hz); 3.3-3.38 (1H, m); 3.53-3.62 (1H, m); 3.78 (2H, d, J=6.18Hz); 3.89-3.97 (3H, m); 4.17 (2H, t, J=7.1Hz); 4.23 (2H, t, J=7Hz); 5.9 (1H, d, J=3.3Hz); 6.04 (1H, d, J=3.36Hz); 6.62 (2H, d, J=8.6Hz); 6.92 (2H, d, J=8.7Hz); 7.09 (2H, d, J=8.58Hz); 7.3 (2H, d, J=8.7Hz) 42. COPh H H H Mol. Wt. = 435 Yield = 45% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7.1Hz); 2.95 (2H, d, J=6.6Hz); 3.3-3.4 (1H, m); 3.51-3.62 (1H, m); 3.95-4.2 (7H, m); 5.66-6.15 (2H, m); 6.72-6.75 (1H, m); 6.74 (2H, d, J=8.5Hz); 6.8-7.96 (7H, m) 43. CH₃ H H

Mol. Wt. = 385 Yield = 60% ¹H:: 0.6-0.62 (2H, m); 0.81-0.84 (2H, m); 1.15 (3H, t, J=6.99Hz); 1.23 (3H, t, J=7.1Hz); 1.7 (1H, m); 2.27 (3H, s); 2.94 (2H, d, J=5.64Hz); 3.3-3.9 (2H, m); 3.95-3.96 (1H, m); 4.12-4.2 (4H, m); 4.32 (2H, t, J=6.43Hz); 5.7 (1H, d, J=3.3Hz); 5.76 (1H, d, J=3.3Hz); 6.76 (2H, d, J=8.61Hz); 7.14 (2H, d, J=8.58Hz) 44. CH₃ H H

Mol. Wt. = 461 Yield = 41.5% ¹H: 1.14 (3H, t, J=6.98Hz); 1.21 (3H, t, J=6.04Hz); 2.39 (3H, s); 2.92 (2H, d, J=6Hz); 3.57-3.32 (2H, m); 3.92 (1H, t, J=3.56Hz); 4.15 (2H, q, J₁=7.13Hz, J₂=7.12Hz); 4.23 (2H, t, J=6.06Hz); 4.53 (2H, t, J=6.05Hz); 5.99 (1H, d, J=3.5Hz); 6.56 (1H, d, J=3.6Hz); 6.69 (1H, s); 6.73 (2H, d, J=8.59Hz); 7.1 (2H, d, J=8.56Hz); 7.54-8.2 (4H, m) 45. CH₃ COOCH₃ H

Mol. Wt = 479 Yield = 33% ¹H: 1.12-1.28 (6H, m); 2.69 (3H, s); 2.91 (2H , d, J=5.8Hz); 3.32 (2H, m); 3.8 (3H, s); 3.8-3.93 (3H, m); 4.11-4.19 (2H, m); 4.3 (2H, t, J=6.18Hz); 6.54-6.61 (3H, m); 7.07 (2H, d, J=8.58Hz); 7.36-7.44 (5H, m) 46. CH₃ H H

Mol. Wt. = 465 Yield = 28% ¹H: 1.15 (3H, t, J=6.99Hz); 1.22 (3H, t, J=7.12Hz), 2.35 (3H, s); 2.92 (2H, d, J=5.91Hz); 3.0-3.8 (2H, m); 3.89-3.95 (3H, m); 4.12-4.17 (2H, q, J₁=7.11Hz, J₂=7.11Hz); 4.25 (2H, t, J=6.72); 5.93 (1H, d, J=3.33Hz); 5.99 (2H, s); 6.03 (1H, d, J=3.39Hz); 6.62 (2H, d, J=8.67Hz); 6.84-6.88 (3H, m); 7 (2H, d, J=8.64Hz) 47. CH₃ H H

Mol. Wt. = 417 Yield = 56% ¹H: 1.16 (3H, t, J=6.16Hz); 1.23 (3H, t, J=7.81Hz); 2.43 (3H, s); 2.87 (2H, d, J=6.84Hz); 2.9-3.3 (2H, m); 3.74 (2H, t, J=6.48Hz); 3.89 (2H, t, J=6.64Hz); 4.1-4.18 (3H, m); 6.06 (1H, d, J=3.33Hz); 6.15 (1H, d, J=3.36Hz); 6.38 (2H, d, J=8.61Hz); 6.98 (2H, d, J=8.58Hz); 7.41-7.9 (7H, m) 48. CH₃ H H

Mol. Wt. = 527 Yield = 42% ¹H: 1.14 (3H, t, J=6.99Hz); 1.22 (3H, t, J=7.14Hz); 2.36 (3H, s); 2.89-2.92 (2H, m); 3.0-3.85 (2H, m); 3.86-3.92 (3H, m); 4.15 (2H, q, J₁=7.14Hz, J₂=7.10Hz); 4.23 (2H, t, J=6.42Hz); 5.08 (2H, s); 5.94 (1H, d, J=3.27); 6.1 (1H, d, J=3.39Hz); 6.6 (2H, d, J=8.61Hz); 6.98-7.05 (3H, m); 7.08 (2H, d, J=8.58Hz); 7.3-7.4 (6H, m) 49. CH₃ H H

Mol. Wt. = 506 Yield = 50% ¹H: 1.15 (3H, t, J=6.99Hz), 1.123 (3H, t J=7.14Hz); 2.35 (3H, s); 2.92 (2H, m); 3.33-3.59 (2H, m); 3.94 (1H, t, J=6.7Hz); 4.04 (2H, t, J=6.22Hz); 4.13-4.2 (2H, q, J₁=7.11Hz, J₂=7.11Hz); 4.31 (2H, t, J=6.24Hz); 5.92 (1H, d, J=3.48Hz); 6.2 (1H, d, J=3.51Hz); 6.7 (2H, d, J=8.61Hz); 6.78 (1H, d, J=3.78Hz); 6.99 (1H, d, J=3.75Hz); 7.12 (2H, d, J=8.58Hz) 50. CH₃ H H

Mol. Wt. = 479 Yield = 60% ¹H: 1.15 (3H, t, J=6Hz); 1.22 (3H, t, J=6Hz); 1.36 (6H, d, J=6.06Hz); 2.36 (3H, s); 2.91 (2H, d, J=7.11Hz); 3.33-3.58 (2H, m); 3.89-3.95 (3H, m); 4.12-4.26 (4H, m); 4.3-4.57 (1H, m); 5.93 (1H, d, J=3.33Hz); 6.04 (1H, d, J=3.39Hz); 6.62 (2H, d, J=8.61Hz); 6.90 (2H, d, J=8.67Hz); 7.07 (2H, d, J=8.55Hz); 7.26 (2H, d, J=8.28Hz) 51. CH₃ H CH₃

Mol. Wt. = 435 Yield = 49% ¹H: 1.15 (3H, t, J=6.9Hz); 1.21 (3H, t, J=7.1Hz); 1.91 (3H, s); 2.33 (3H, s); 2.90 (2H, d, J=7.02Hz) 3.32-3.58 (2H, m); 3.83 (2H, t, J=6.67Hz); 3.90-3.95 (1H, m); 4.10-4.19 (4H, m); 5.84 (1H, s); 6.54 (2H, d, J=8.64Hz); 7.05 (2H, d, J=8.61Hz); 7.30-7.42 (5H, m) 52. CH₃ H H

Mol. Wt. = 427 Yield = 42% ¹H: 1.15 (3H, t, J=6.9Hz), 1.23 (3H, t, J=7Hz), 2.36 (3H, s); 2.9 (2H, m), 3.3 (1H, m) 3.6 (1H, m); 3.9 (1H, m); 4.05 (2H, t, J=6.4Hz), 4.12-4.2 (2H, q, J₁=J₂=7Hz); 4.3 (2H, t, J=6.4Hz); 5.9 (1H, d, J=3.5Hz); 6.2 (1H, d, J=3.5Hz); 6.6 (2H, d, J=8.6Hz); 7.0-7.1 (2H, m), 7.12-7.15 (2H, m); 7.25-7.27 (1H, m) 53. CH₃ H H

Mol. Wt. = 527 Yield = 52% ¹H: 1.15 (3H, t, J=6.9Hz); 1.23 (3H, t, J=6.9); 2.3 (3H, s); 2.90-2.93 (2H, m); 3.3 (1H, m); 3.55 (1H, m); 3.9 (2H, m) 4.1-4.15 (3H, m); 4.2 (2H, m); 5.1 (2H, s); 5.9 (1H, d, J=3.3Hz); 6.0 (1H, d, J=3.3Hz); 6.6 (2H, d, J=8.5Hz); 6.99 (2H, d, J=8.5Hz); 7.1 (2H, d, J=8.5Hz); 7.3-7.47 (7H, m) 54. CH₃ H H

Mol. Wt. = 437 Yield = 50% ¹H: 1.17 (3H, t, J=6.9Hz); 1.23 (3H, t, J=7Hz); 2.3 (3H, s); 2.9 (2H, m); 3.3 (1H, m); 3.6 (1H, m); 3.9-4.0 (3H, m); 4.1-4.2 (4H, m); 5.9 (1H, d, J=3.3Hz); 6.0 (1H, d, J=3.3Hz); 6.5 (2H, d, J=8.6Hz); 6.8 (2H, d, J=8.6Hz); 7.0 (2H, d, J=8.6Hz); 7.2 (2H, d, J=8.6Hz) 55. H H H C₆H₅ Mol. Wt. = 407 Yield = 99% ¹H: 1.1 (3H, t, J=6.9Hz); 1.22 (3H, J=7.11Hz); 2.9 (2H, m); 3.3-3.4 (1H, m); 3.55-3.6 (1H, m); 3.9 (1H, m); 4.08 (2H, t, J=6.1Hz); 4.12-4.17 (2H, q, J₁=J₂=7.1Hz); 4.3 (2H, t, J=5Hz); 6.0 (2H, m); 6.6 (2H, d, J=8.6Hz); 6.9 (1H, m); 7.0 (2H, d, J=8.6Hz); 7.1-7.4 (5H, m) 56. CH₃ H H

Mol. Wt. = 461.5 Yield = 60% ¹H: 1.1 (3H, t, J=6.9Hz); 1.23 (3H, t, J=7Hz); 2.36 (3H, s); 2.9 (2H, m); 3.3 (1H, m); 3.6 (1H, m); 3.9 (1H, t, J=5.9Hz); 4.05 (2H, t, J=6.1Hz); 4.16 (2H, q, J=7Hz); 4.3 (2H, t, J=6.3Hz), 5.9 (1H, d, J=3.5Hz); 6.2 (1H, d, J=3.5Hz); 6.6 (2H, d, J=8.6Hz); 6.8 (1H, d, J=3.8); 6.86 (1H, d, J=3.8Hz); 7.12 (2H, d, J=8.58Hz) 57. CH₃ H H

Mol. Wt. = 465 Yield = 56% ¹H: 1.15 (3H, t, J=7.14Hz); 1.2 (3H, t, J=7.14Hz); 1.45 (3H, t, J=6.99Hz); 2.36 (3H, s); 2.9 (2H, d, J=5.97Hz); 3.35 (1H, m); 3.6 (1H, m); 3.91 (3H, m); 4.15 (4H, m); 4.23 (2H, m); 5.94 (1H, d, J=3.30Hz); 6.05 (1H, d, J=3.33Hz); 6.62 (2H, d, J=8.64Hz); 6.92 (2H, d, J=6.78Hz); 7.08 (2H, d, J=8.64Hz); 7.3 (2H, d, J=6.69Hz) 58. CH₃ H H

Mol. Wt. = 441 Yield = 53% ¹H: 1.15 (3H, t, J=6.99Hz); 1.23 (3H, t, J=7Hz); 2.36 (3H, s); 2.48 (3H, s); 2.93 (2H, d, J=6.17Hz); 3.33-3.59 (2H, m); 3.9 (1H, t, J=6.6Hz); 4.05 (2H, t, J=6.4Hz); 4.15 (2H, t, J₁=6.4Hz, J₂=7Hz); 4.32 (2H, l, J=6.4Hz); 5.91 (1H, d, J=3.38Hz); 6.17 (1H, d, J=3.4Hz), 6.68-6.71 (3H, m); 6.8 (1H, d), 7.1 (2H, d, J=8.2Hz) 59. CH₃ CH₃ H C₆H₅ Mol. Wt. = 435 Yield = 51% ¹H: 1.15 (3H, t, J=7Hz) Hz; 1.22 (3H, t, J=7Hz); 2.05 (3H, s); 2.27 (3H, s); 2.9 (2H, m); 3.3 (1H, m), 3.5 (1H, m); 3.9 (3H, m); 4.1 (2H, m); 4.26 (2H, t, J=6.6Hz); 6.0 (1H, s); 6.6 (2H, d, J=8.6Hz); 7.05 (2H, d, J=8.5Hz); 7.26 (1H, m); 7.29-7.35 (4H, m) 60. CH₃ H H

Mol. Wt. = 451 Yield = 70% ¹H: 1.15 (3H, t, J=6.9Hz); 1.22 (3H, t, J=7Hz); 2.37 (3H, s); 2.9-2.95 (2H, m); 3.29-3.38 (1H, m); 3.55-3.63 (1H, m); 3.8 (3H, s); 3.94 (3H, t, J=6.24Hz); 4.17 (2H, q, J=7.1Hz); 4.3 (2H, t, J=6.6Hz); 5.96 (1H, d, J=2.8Hz); 6.12 (1H, d, J=3.39Hz); 6.69 (2H, d, J=8.6Hz); 6.88-7.0 (2H, m); 7.09 (2H, d, J=8.6Hz); 7.26-7.31 (2H, m) 61. CH₃ H H

Mol. Wt. = 427 Yield = 54% ¹H: 1.16 (3H, t, J=6.9Hz); 1.23 (3H, t, J=7Hz); 1.3-1.88 (10H, m); 2.27 (3H, s); 2.51-2.53 (1H, m): 2.92-2.95 (2H, m); 3.3-3.4 (1H, m); 3.53-3.63 (1H, m); 3.95 (1H, t, J=5.9Hz); 4.0-4.1 (2H, m); 4.1-4.22 (4H, m); 5.8 (1H, d, J=3.4Hz); 5.84 (1H, d, J=3.3Hz); 6.7 (2H, d, J=8.6Hz); 7.13 (2H, d, J=8.5Hz)

PREPARATION 10 (S)-Ethyl[3-{4-[2-(5-methyl-2-quinolinyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate (Example 62)

A mixture of diketo compound (0.8 g), pivalic acid (0.06 g), amino ester (0-4 g) in toluene (20 ml.) was heated to reflux for 3 hours with continuous removal of water using a Dean-Stark apparatus. Later it was cooled to 20-25° C. and toluene was distilled at reduced pressure. To the residue was added D.M. water (20 ml) and crude product was distilled at ethylacetate (2×30 ml), washed with water (2×30 ml) and saturated brine solution (30 ml). Organic layer was dried over Na₂SO₄ to obtain brown thick oil (0.32 g), The crude product was purified by column chromatography using sillica gel (100-200) and ethyl acetate:PET ether(1:9) as an eluent to afford yellowish thick oil (0.1 g).

In like manner to that described in preparation 10, the following compounds of general formula (I) were prepared.

TABLE 8 Ex. Substituents on the pyrrole ring in (I) No. R₁ R₂ R₃ R₄ 62. CH₃ H H

Mol. Wt. = 472 Yield = 35% ¹H: 1.14(3H, t, J=6.99Hz); 1.23(3H, t, J=7.14Hz); 2.4(3H, s); 2.89-2.92(2H, m); 3.28-3.38(1H, m); 3.52-3.6(1H, m); 3.9-3.95 (1H, m); 4.14(2H, q, J₁=7.08Hz, J₂=7.08Hz); 4.45(2H, t, J=5.76Hz); 5.02(2H, t, J=5.79Hz); 6.02(1H, d, J=3.72Hz); 6.75-6.78(3H, m); 7.10(2H, d, J=8.6Hz); 7.4-7.7(4H, m); 7.89(1H, d, J=8.3Hz); 8.0(1H, d, J=8.7Hz) 63. CH₃ H H

Mol. Wt. = 422 Yield = 23% ¹H: 1.15(3H, t, J=6.99Hz); 1.23(3H, t, J=7.14Hz); 2.39(3H, s); 2.91(2H, d, J=7.44Hz); 3.58-3.80(2H, m); 3.93(1H, t, J=6.63Hz); 3.99(2H, t, J=6.12Hz); 4.12-4.20(2H, q, J₁=7.11Hz, J₂=7.11Hz); 4.38(2H, t, J=6.12Hz); 6.01(1H, d, J=3.45Hz); 6.30(1H, d, J=3.54Hz); 6.63(2H, d, J=8.61Hz); 7.10(2H, d, J=8.55Hz); 7.33 (2H, d, J=6Hz); 8.58(2H, d, J=5.89Hz) 64. CH₃ H H

Mol. Wt. = 422 Yield = 21% ¹H: 1.15(3H, t, J=7Hz); 1.22(3H, t, J=6.9Hz); 2.39(3H, s); 2.91 (2H, d, J=7.02Hz); 3.32-3.57(2H, m); 3.94(1H, t, J=6.63Hz); 4.15 (2H, q, J₁=7.14Hz, J₂=7.11Hz); 4.25(2H, t, J=6.06Hz); 4.81(2H, t, J=6.07Hz); 5.95(1H, d, J=3.21Hz); 6.53(1H, d, J=3.63Hz); 6.75(2H, d, J=8.49Hz); 7.02-7.08(1H, m); 7.10(2H, d, J=8.64); 7.51(1H, d, J=8.07Hz); 7.5-7.6(1H, m); 8.49-8.50(1H, m) 65. CH₃ H H

Mol. Wt. = 422 24% ¹H: 1.15(3H, t, J=7Hz); 1.23(3H, t, J=7.11Hz); 2.38(3H, s); 2.91 (2H, t, J=3.78Hz); 3.32-3.58(2H, m); 3.9-3.97(3H, m); 4.16(2H, q, J₁=7.11Hz, J₂=7.11Hz); 4.29(2H, t, J=6.15Hz); 6.0(1H, d, J=3.45Hz); 6.17(1H, d, J=3.48Hz); 6.62(2H, d, J=8.64Hz); 7.09 (2H, d, J=8.58Hz); 7.32-7.34(1H, m); 7.71-7.74(1H, m); 8.53-8.55 (1H, m); 8.68-8.69(1H, m)

PREPARATION 11 (R/S) Methyl-2-ethoxy-3[6-[2-[2-(4-methoxyphenyl)-5-methyl-pyrol-1-yl]ethoxy]napthalen-2-yl]propanoate (Example 66)

A mixture of (R/S)-ethyl 3-(4-hydroxynapthyl)-2-ethoxypropionate (1 g) and dry potassium carbonate (0.7 g) in dimethyl formamide (20 mL) was stirred at 80° C. for 30 min. Compound. No. 69 (1.2 g) was added at 40° C. and stirring was continued at 80° C. for 24 h. The reaction mixture was cooled to 20° C.-25° C. and 20 mL water was added. The reaction mixture was extracted with ethyl acetate (2×30 mL), washed with water (2×30 mL), brine (30 mL) and was dried over sodium sulfate. The organic layer was evaporated under reduced pressure to obtain an oily product. The crude oily product was chromatographed over silica gel (100-200 mesh) using ethyl acetate:petroleum ether (1:9) as an eluent to afford the title compound as a yellow oil (0.6 g 31%).

TABLE 9 Ex. Substituents on the pyrrole ring in (I) No. R¹ R² R³ R⁴ 66. CH₃ H H

Mol. Wt. = 487 Yield = 31% ¹H: 1.14(3H, t, J=7Hz) Hz; 2.4(3H, s); 3.1-3.16(2H, m); 3.3-3.8 (1H, m); 3.55-3.64(1H, m); 3.68(3H, s); 3.84(3H, s); 4.03-4.41 (3H, m); 4.32(2H, t, J=6.6Hz); 5.96(1H, d, J=3.36Hz); 6.0(1H, d, J=3.39Hz); 6.8(1H, d, J=2.37Hz); 6.9-7.0(3H, m); 7.33-7.38(3H, m); 7.52-7.64(3H, m)

PREPARATION 12 (S)-Methyl 3-{4-[2-(2-phenyl-5-methyl pyrrol-1-yl)ethoxy]phenyl-}-2-methoxypropanoate (Example

Using a similar procedure to that described in preparation 7, (S)-methyl 3-(4-hydroxy phenyl)-2-methoxypropanoate (3.3 g), and mesylate (Compound No. 64 (table 5), 4.38 g), gave the titled compound (12 g, 20%).

In the like manner to that described in above example, the corresponding propoxy derivative (Example no. 68) was prepared using (S)-Propyl 3-(4-hydroxyphenyl)-2-propoxy propionate and mesylate (given in the Table 5).

TABLE 10 (I)

Substituents on Ex. the pyrrole ring in (I) No. R¹ R² R³ R⁴ 67. CH₃ H H

R = CH₃ Mol. Wt. = 393 Yield = 20% ¹H: 2.37(3H, s); 2.9-3(2H, m); 3.33(3H, s); 3.71(3H, m); 3.92(3H, t, J=6.96Hz); 4.29(2H, t, J=6.6Hz); 5.97(1H, d, J=3.36Hz); 6.11 (1H, d, J=3.39Hz); 6.6(2H, d, J=8.67Hz); 7.05(2H, d, J=8.64Hz); 7.30-7.40(5H, m). 68. CH₃ H H

R = C₃H₇ Mol. Wt. = 449 Yield = 20% ¹H: 0.83(3H, t, J=7.4Hz); 0.89(3H, t, J=7.4Hz); 1.53-1.63(4H, m); 2.37(3H, s) 2.91(2H, d, J=5.54Hz); 3.20-3.48(2H, m); 3.92(3H, t, J=6.59Hz); 4.06(2H, t, J=6.67Hz); 4.28(2H, t, J=7.4Hz); 5.97(1H, d, J=3.39Hz); 6.11(1H, d, J=3.4Hz); 6.59(2H, d, J=8.64Hz); 7.07 (2H, d, J=8.63Hz); 7.25-7.4(5H, m).

PREPARATION NO. 13 Ethyl (E/Z) 2-ethoxy-3-[4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl]prop-2-enoate (Example 69)

To a solution of triethyl 2-ethoxyphosphonoacetate (12.5 g) in dry, THF (60 mL) was added slowly to a well-stirred ice-old suspension of NaH (1-8 g, 60% dispersion in oil) in dry THF (60 mL) under N₂ atmosphere. The reaction mixture was stirred at 0° C. for 30 min. and 4-[2-(5-methyl-2-phenylpyrrol-1-yl) ethoxy]benzaldehyde (compound no. 113) (10.8 g) in dry THF (80 mL) was added. The mixture was allowed to warm up to 20° C. to 25° C. and stirred for 3.5 hrs. The solvent was evaporated and the residue was diluted with water (150 mL) further the product was extracted with ethyl ace (2×150 mL). The combined extracts washed with water (150 mL), brine (50 mL), and was dried over sodium sulfate. The solvent was evaporated under reduced pressure to afford crude product. The crude product was chromatographed over silica gel using pet. ether:ether (9:1) as an eluent to afford E and Z isomers, which were isolated by removing the of solvents.

TABLE 11 Substituents Ex. on the pyrrole ring No. R¹ R² R³ R⁴ 69. CH₃ H H Phenyl Mol. Wt. = 419 Yield 40% E/Z-isomer 70. CR₃ H H Phenyl Mol. Wt. = 419 Yield = 15% E-isomer ¹H: 1.13(3H, t, J=7.14Hz); 1.4(3H, J=6.9Hz); 2.3(3H, s); 3.86-3.95(4H, m); 4.13(2H, q, J=7.1Hz); 4.27-4.31(2H, t, J=6.6Hz); 5.96(1H, d, J=3.3Hz); 6.03(1H, s); 6.11(1H, d, J=3.3Hz); 6.5-6.6(2H, d, J=8.7Hz); 7.03-7.06(2H, d, J=8.5Hz) 7.32-7.34(1H, m); 7.35-7.41(4H, m). 71. CH₃ H H Phenyl Mol. Wt. = 419 Yield = 15% Z-isomer ¹H: 1.33-1.38(6H, t, J=7.0Hz); 2.38(3H, s); 3.92-3.99(4H, m); 4.24-4.33(4H, m); 5.98(1H, d, J=3.3Hz); 6.11(1H, d, J=3.3Hz); 6.63-6.6(2H, d, J=8.9Hz); 6.92(1H, s); 7.33(1H, m); 7.36-7.41(4H, m); 7.64-7.67(2H, d, J=8.8Hz).

PREPARATION 14 (R/S) Methyl 2-ethoxy-3[4-[2-[2-methyl-5-phenyl-1H-pyrrol-1-yl]ethoxy]phenyl]propanoate (Example 72)

Mixture of E/Z compounds (Example no. 70 and 71) obtained in preparation 13 (7.1 g, 0.016 mole) and magnesium turnings (73 g, 0.3 mole) in dry methanol (70 mL) was stirred at 25° C. for 3.5 hrs. H₂O (150 mL) was added and pH of the reaction mixture was adjusted in 2-3 with 35% hydrochloric acid. The product was extracted in ethyl acetate (2×100 mL) combined extract was washed with H₂O (2×100 mL) brine (100 mL) and dried over Na₂SO₄. The extract was concentrated under reduced pressure. The crude product was chromatographed over silica gel using pet. ether:ether (9:1) as an eluent. The product obtained racemic mixture but the ethyl ester was converted to methyl ester.

Alternatively, the E and Z compound mixture is hydrogenated in the presence of 10% Pd/C catalyst at 60 psi pressure to obtain the title compound.

TABLE 12 Substituents Ex. on the pyrrole ring No. R¹ R² R³ R⁴ 72. CH₃ H H Phenyl Mol. Wt. = 407 Yield = 50% ¹H: 1.15(3H, t, J=7.0Hz); 2.37(3H, s,); 2.90-2.92(2H, dd); 3.32-33.5(1H, m); 3.55-3.57(1H, m); 3.69(3H, s); 3.90-3.97 (3H, m); 4.29(2H, t, J=6.9Hz); 5.9(1H, d, J=3.4Hz); 6.1(1H, d, J=3.4Hz); 6.59(2H, d, J=8.6Hz); 7.05(2H, d, J=8.5Hz); 7.26-7.41(5H, m).

PREPARATION 15 (S)-3-{4-[2-(5-Ethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid (Example 96)

A mixture of substituted ester (prepared in example 24) (1.3 g), sodium hydroxide (0.24 g in 5 mL D. M. water) in methanol (10 mL) was stirred at 20° C. to 25° C. for 10 h. Methanol was evaporated under reduced pressure. The residue was diluted with water (10 mL) and was acidified with dilute hydrochloric acid. The product was extracted with ethyl acetate (3×20 mL) and washed with water (2×30 mL), brine (30 mL) and was dried over sodium sulfate to obtain an oily product (1.17 g, 96%). The crude product (3 g) was used in next step without purification.

In like manner to that described in Preparation 15 above following compounds of the formula (I) (given in Table 13) were prepared from the appropriately substituted pyrrole derivatives described elsewhere:

TABLE 13 (I)

Ex. Substituents on the pyrrole ring in (I) No. R¹ R² R³ R⁴  73. CH₃ H CH₃ H Mol. Wt. = 331 Yield = 88% ¹H: 0.96(3H, t, J=6.76Hz); 1.9(3H, s); 2.13(3H, s); 2.78(2H, m); 3.3-3.6(2H, m); 4.05 (5H, m); 5.53(1H, s); 6.43(1H, s) 6.75(2H, d, J=9.0Hz); 7.07(2H, d, J=9.0Hz).  74. C₂H₅ H H H Mol. Wt. = 331 Yield = 10% ¹H: 1.16(3H, t, J=6.9Hz); 1.27(3H, t, 3.51Hz); 2.62(2H, q); 2.5(2H, m); 3.44-3.46 (2H, m); 4.03(1H, dd, J₁=4.23Hz, J₂=4.5Hz); 4.13(2H, t, J=5.2Hz); 4.18(2H, t, J=3.76Hz); 5.91-5.92(1H, m); 6.10(1H, t, J=3.12Hz); 6.70(1H, d, J=2.01Hz); 6.77(2H, d, J=8.7Hz); 7.135(2H, d, J=8.64Hz).  75. CHO H H H Mol. Wt. = 331 Yield = 75% ¹H: 1.10(3H, t, J=7Hz); 2.8-4.0(5H, m); 4.16(2H, t, J=4.9Hz); 4.65(2H, t, J=4.9Hz); 6.22(1H, dd); 6.7(2H, d, J=8.5Hz); 6.97(1H, dd); 7.1-7.14(1H, m); 7.14(2H, d, J=8.5Hz); 9.49(1H, s).  76. COCH₃ H H H Mol. Wt. = 345 Yield = 10% ¹H: 0.87(3H, t, J=6.87Hz); 2.39(3H, s); 2.66(2H, dd, J=11.55Hz); 2.95-3.06(2H, m); 3.73(1H, t, J=4.5Hz); 4.09(2H, t, J=4.74Hz); 4.60(2H, t, J=4.89Hz); 6.08(1H, dd, J₁=2.64Hz, J₂=2.64Hz); 6.58(2H, d, J=8.37Hz); 6.92-6.99(2H, m); 7.00(2H, d, J=8.34Hz).  77. CH₃ H H CH₂CH₃ Mol. Wt. = 345 Yield = 54% ¹H: 1.16(3H, t, J=7Hz); 1.28(3H, t, J=7Hz); 2.28(3H, m); 2.55(2H, t, J=7.4Hz); 3.06(2H, dd); 3.4-3.62(2H, m); 4.0-4.16(5H, m); 5.8-5.84(2H, m); 6.75(2H, d, J=6.78Hz); 7.14(2H, d, J=6.78Hz).  78. CH₃ H H (CH₂)₂CH₃ Mol. Wt. = 423 Yield = 66% ¹H: 1.02(3H, t, J=6.9Hz); 1.17(3H, t, J=6.9Hz); 1.7(2H, sextet); 2.28(3H, s); 2.55 (2H, t, J=7.7Hz); 2.94(1H, dd); 3.4(1H, dd); 3.4-3.62(2H, m); 4.0-4.2(5H, m); 5.8-5.84(2H, m); 6.75(2H, d, J=8.5Hz); 7.14(2H, d, J=8.5Hz).  79. CH₃ H H (CH₂)₃CH₃ Mol. Wt. = 373 Yield = 76% ¹H: 0.95(3H, t, J=7.2Hz); 1.17(3H, t, J=7.0Hz); 1.4-1.5(2H, m); 1.6-1.7(2H, m); 2.28(3H, s); 2.57(2H, t, J=7.7Hz); 2.95(1H, dd); 3.07(1H, dd); 3.4-3.5(1H, m); 3.53-3.62 (1H, m); 4.0-4.2(5H, m); 5.8-5.83(2H, m); 6.77(2H, d, J=8.5Hz); 7.15(2H, d, J=8.5Hz).  80. CH₃ H H

Mol. Wt. = 393 Yield = 96% ¹H: 1.16(3H, t, J=6.9Hz); 2.37(3H, s); 2.92-3.02(2H, dd, J₁=7Hz, J₂=4.2Hz); 3.41- 3.58(2H, m); 3.92(2H, t); 3.98-4.01(1H, m); 4.1-4.3(2H, t, J=6.5Hz); 5.96(1H, d, J=3.3Hz); 6.1(1H, d, J=3.3Hz); 6.6(2H, d, J=8.5Hz); 7.0(2H, d, J=8.5Hz); 7.06-7.09 (2H, d, J=8.6Hz); 7.2-7.4(5H, m).  81. CH₃ H

H Mol. Wt. = 393 Yield = 96% ¹H: 1.12(3H, t, J=6.9Hz); 2.37(3H, s); 2.92-3.02(2H, dd, J₁=7Hz, J₂=4.2Hz); 3.41-3.58(2H, m); 3.92(2H, t); 3.98-4.01(1H, m); 4.1-4.3(2H, t, J=6.5Hz); 5.96(1H, d, J=3.3Hz); 6.1(1H, d, J=3.3Hz); 6.6(2H, d, J=8.5Hz); 7.0(2H, d, J=8.5Hz); 7.2-7.4(5H, m).  82. CH₃ H H

Mol. Wt. = 407 Yield = 75% ¹H: 1.02(3H, t, J=6.9Hz); 2.34(3H, s); 2.36(3H, s); 2.74(1H, dd); 3.0(1H, dd); 3.19-3.22 (1H, m); 3.4-3.45(1H, m); 3.78-3.79(1H, m); 3.8(2H, t, J=6.4Hz); 4.25(2H, t, J=6.4Hz); 5.96(1H, d, J=3.36Hz); 6.07(1H, d, J=3.36Hz); 6.6(1H, d, J=8.5Hz); 7.09(2H, d, J=8.5Hz); 7.19(2H, d, J=8.5Hz); 7.28(2H, d, J=8.5Hz).  83. CH₃ H H

Mol. Wt. = 407 Yield = 100% ¹H: 1.08(3H, t, J=6.99Hz); 2.33(3H, s); 2.35(3H, s); 2.62(2H, m); 3.28-3.31(2H, m); 3.71 (1H, m); 3.90(2H, t, J=6.0Hz); 4.3(2H, t, J=6.05Hz); 5.86(1H, d, J=3.33Hz); 5.96(1H, d, J=3.4Hz); 6.57(2H, d, J=8.6Hz); 7.09(2H, d, J=8.6Hz); 7.13-7.29(4H, m).  84. CH₃ H H

Mol. Wt. = 407 Yield = 85% —  85. CH₃ H H

Mol. Wt. = 423 Yield = 62% ¹H: 1.077(3H, t, J=7Hz); 2.368(3H, s); 2.93(3H, s); 2.94(1H, m); 3.35-3.5(2H, m); 3.78(1H, t, J=7.1Hz); 3.8(3H, m); 3.9(2H, t, J=7Hz); 4.25(2H, t, J=7Hz); 5.9(1H, d, J=3.36Hz); 6.0(1H, d, J=3.36Hz); 6.64(2H, d, J=8.5Hz); 7.1(2H, d, J=8.5Hz); 7.31 (2H, d, J=6.78Hz).  86. CH₃ H H

Mol. Wt. = 472 Yield = 84% ¹H: 1.02(3H, t, J=6.9Hz); 2.353(3H, s); 2.74(1H, dd); 2.95(1H, dd); 3.19-3.28(1H, m); 3.4-3.45(1H, m); 3.8(1H, dd); 3.9(2H, t, J=6.21Hz); 4.26(2H, t, J=6.2Hz); 5.9 (1H, d, J=3Hz); 6.1(1H, d, J=3.4Hz); 6.6(2H, d, J=8.5Hz); 7.1(2H, d, J=8.5Hz); 7.29(2H, d, J=8.5Hz); 7.5(2H, d, J=8.5Hz).  87. CH₃ H H

Mol. Wt. = 419 Yield = 77% ¹H: 1.02(3H, t, J=6.9Hz); 2.3(3H, s); 2.7-2.8(1H, m); 2.96(1H, m); 3.8(1H, m); 3.1-3.2 (1H, m); 3.4-3.5(1H, m); 3.86-3.91(2H, t, J=6.3Hz); 4.2-4.24(2H, t, J=6.3Hz); 5.9(1H, d, J=3.3Hz); 6.05(1H, d, J=3.3Hz); 6.56-6.59(2H, d, J=8.6Hz); 7.05-7.09 (4H, m); 7.28-7.37(2H, m).  88. CH₃ H H

Mol. Wt. = 427.5 Yield = 37% —  89.

H CH₃ H Mol. Wt. = 393 Yield = 41% —  90. CH₃ H

Mol. Wt. = 469 Yield = 83% ¹H: 1.16(3H, t, J=7Hz); 2.41(3H, s); 2.9(1H, dd); 3.05(1H, dd); 3.4-3.6(2H, m); 3.9(2H, t, J=6.5Hz); 4.03(1H, dd); 4.16(2H, t, J=6.5Hz); 6.2(1H, s); 6.5-7.4(14H, m).  91. i-Pr H H i-Pr Mol. Wt. = 387 Yield = 50% ¹H: 1.19(3H, t, J=6.8Hz); 1.24-1.26(12H, d, J=6.7Hz); 2.92-2.99(4H, complex); 3.40 (1H, m); 3.6(1H, m); 4.03(3H, complex); 4.24(2H, t, J=Hz); 5.87(2H, s); 6.75-6.76 (2H, d, J=8.8Hz); 7.13-7.15(2H, d, J=8.6Hz).  92. i-Pr H H

Mol. Wt. = 443 Yield = 87% ¹H: 0.94(3H, t, J=7.29Hz); 1.22(6H, d, J=7.29Hz); 2.49-2.51(2H, dd, J=6.75Hz); 3.03-3.08(2H, m); 3.45-3.55(2H, m); 3.82(2H, t, J=5.91Hz); 4.29(2H, t, J=5.92Hz); 5.85 (1H, d, J=3.51Hz); 5.95(1H, d, J=3Hz); 6.52(2H, d, J=8.58Hz); 7.01(2H, d, J=8.52 Hz) 7.29-7.40(5H, m)  93. i-Pr

H

Mol. Wt. = 558 Yield = 50% ¹H: 1.18(3H, t, J=6.9Hz); 1.51-1.53(6H, d, J=7Hz); 2.9-3.1(2H, m); 3.5-3.6(3H, Complex); 3.92(2H, t, J=6.2Hz); 4.05(1H, m); 4.3(2H, t, J=6.2Hz); 6.31(1H, s); 6.58-6.60 (2H, d, J=6.7Hz); 7.1(4H, m); 7.30-7.38(4H, m); 7.5(1H, s); 7.58-7.59(2H, d)  94. SCH₃ H H H Mol. Wt. = 349 Yield = 93% ¹H: 1.18(3H, t, J=7Hz); 2.29(3H, s); 2.9-3.1(2H, m); 3.4-3.6(2H, m); 4.0-4.04(1H, m); 4.2(2H, t, J=5.6Hz); 4.42(2H, t, J=5.6Hz); 6.1(1H, t, J=3.2Hz); 6.38(1H, dd); 6.8(2H, d, J=8.5Hz); 6.95(1H, dd); 7.15(2H, d, J=8.5Hz).  95. C₂H₅ H H C₂H₅ Mol. Wt. = 359 Yield = 99% ¹H: 1.16(3H, t, J=6.8Hz); 1.29(6H, t, J=7.4Hz); 2.65(4H, q, J=7.4Hz); 2.94-3.05(2H, m); 3.39-3.49(1H, m); 3.51-3.6(1H, m); 4.01-4.07(3H, m); 4.15(2H, t, J=5.8Hz); 5.86 (2H, s); 6.7(2H, d, 8.5Hz); 7.15(2H, d, J=8.5Hz)  96. C₂H₅ H H C₆H₅ Mol. Wt. = 407 Yield = 90% ¹H: 1.16(3H, t, J=6.99Hz); 1.34(3H, t, J=7.4Hz); 2.73-2.78(2H, q, J=7.5Hz,); 2.9-3.9 (2H, m); 3.4-3.48(1H, m); 3.52-3.6(1H, m); 3.9(2H, t, J=6.63Hz); 4.0-4.05(1H, m); 4.3 (2H, t, 6.75Hz); 6.0(1H, d, J=3.48Hz); 6.15(1H, d, J=3.5Hz); 6.6(2H, d, J=8.5Hz); 7.08 (2H, d, J=8.6Hz); 7.3-7.4(5H, m)  97. CH₃ H H

Mol. Wt. = 421 Yield = 98% ¹H: 1.16(3H, t, J=6.9Hz); 2.29(3H, s); 2.88-3.04(6H, m); 3.38-3.48(1H, m); 3.53-3.62 (1H, m); 3.99-4.07(3H, m); 4.15(2H, t, J=7Hz); 5.85(1H, d, J=3.3Hz); 5.9(1H, d, J=3.3Hz); 6.7(2H, d, J=8.6Hz); 7.14(2H, d, J=8.6Hz); 7.2-7.3(5H, m)  98. CH₃ H H

Mol. Wt. = 423 Yield = 90% ¹H: 1.15(3H, t, J=6.9Hz; 2.24(3H, s); 2.89-2.95(2H, m); 3.3-3.58(2H, m); 3.67(3H, s); 3.78-4.17(3H, m); 4.28(2H, t, J=6Hz); 5.89(1H, d, J=3.1.Hz); 6.06(1H, d, J=3Hz); 6.49-7.21(8H, m)  99. CH₃ H H

Mol. Wt. = 399 Yield = 92% ¹H: 1.17(3H, t, J=6.9Hz); 1.3-1.4(6H, m); 1.75-2.5(5H, m); 2.27(3H, s); 2.9-3.08(2H, m); 3.38-3.45(1H, m); 3.57-3.65(1H, m); 3.98-4.15(3H, m); 4.2(2H, t, J=7.2Hz); 5.8 (1H, d, J=3.4Hz); 5.84(1H, d, J=3.3Hz); 6.78(2H, d, J=8.5Hz); 7.17(2H, d, J=8.5Hz) 100. CH₃ H H

Mol. Wt. = 469 Yield = 85% ¹H: 1.16(3H, t, J=6.9Hz); 2.33(3H, s); 2.9-3.0(2H, m); 3.38-3.48(1H, m); 3.55-3.66(1H, m); 3.88-3.94(1H, m); 3.99(2H, t, J=5.8Hz); 4.3(2H, t, J=6.3Hz); 5.91(1H, d, J=3.3Hz); 6.07(1H, d, J=3.4Hz); 6.63(2H, d, J=8.5Hz); 7.1(2H, d, J=8.5Hz); 7.3-7.5(5H, m); 7.68 (4H, d, J=8.2Hz) 101. CH₃ H H

Mol. Wt. = 383 Yield = 92% ¹H: 1.16(3H, t, J=6.99Hz); 2.32(3H, s); 2.9-3.0(2H, m); 3.38-3.48(1H, m); 3.55-3.64 (1H, m); 4.00-4.04(1H, dd, J=4.2Hz); 4.15(2H, t, J=5.98Hz); 4.38(2H, t, J=6.1Hz); 5.9 (1H, d, J=3.48Hz); 6.32(1H, d, J=3.55Hz); 6.35(1H, d, J=3.5Hz); 6.42-6.43(1H, m); 6.7 (2H, d, J=8.5Hz); 7.14(2H, d, J=8.5Hz); 7.4-7.41(1H, m) 102. CH₃ H H

Mol. Wt. = 439 Yield = 99% ¹H: 1.14(3H, t, J=6.9Hz); 2.37(3H, s); 2.48(3H, s); 2.92-3.06(2H, m); 3.32-3.42(1H, m); 3.57-3.64(1H, m); 3.9(2H, t, J=6.36Hz); 4.0(1H, dd); 4.28(2H, t, J=6.z); 5.9(1H, d, J=3.3Hz); 6.08(1H, d, J=3.38Hz); z); 6.6(2H, d, J=8.5Hz); 7.1(2H, d, J=8.5Hz); 7.26 (2H, d, J=8.4Hz); 7.3(2H, d, J=8.34Hz) 103. CH₃ H H

Mol Wt. = 397 Yield = 95% ¹H: 1.07(3H, t, J=6.97Hz); 2.27(3H, s); 2.3(3H, s); 2.7-2.8(1H, m); 2.89-2.96(1H, m); 3.2-3.3(1H, m); 3.5-3.6(1H, m); 3.76-3.8(1H, m); 4.12(2H, t, J=5.8Hz); 4.35(2H, t, J=5.9Hz); 5.79-5.81(1H, dd, J=0.69Hz, J=0.69Hz); 6.01-6.02(1H, dd, J=1,1Hz); 6.15 (1H, d, J=3.5Hz); 6.2(1H, d, J=3.1Hz); 6.7(2H, d, 8.6)Hz; 7.14(2H, d, J=8.6Hz) (solvent used is CD₃OD) 104. CH₃ H H

Mol. Wt. = 418 Yield = 85% ¹H: 1.069(3H, t, J=6.9Hz); 2.34(3H, s); 2.74-2.8(2H, m); 3.2-3.25(1H, m); 3.5-3.58 (1H, m); 3.76-3.8(1H, dd); 3.93(2H, t, J=5.58Hz); 4.37(2H, t, J=5.56Hz); 5.9(1H, d, J=3.3Hz); 6.16(1H, d, J=3.5Hz); 6.57(2H, d, J=8.5Hz); 7.1(2H, d, J=8.5Hz); 7.56(2H, d, J=8.57Hz); 7.68(2H, d, J=8.59Hz) (solvent used is CD₃OD) 105. CH₃ H H

Mol. Wt. = 485 Yield = 92% ¹H: 1.07(3H, t, J=6.96Hz); 2.33(3H, s); 2.7-2.95(2H, m); 3.2-3.35(1H, m); 3.5-3.6(1H, m); 3.76-3.8(1H, m); 3.94(2H, t, J=5.9Hz); 4.28(2H, t, J=5.9Hz); 5.86(1H, d, J=3.1Hz); 5.96(1H, d, J=3.4Hz); 6.6(2H, d, J=8.5Hz); 7.08-7.37(11H, m) (solvent used is CD₃OD) 106. CH₃ H H

Mol. Wt. = 535 Yield = 80% ¹H: 1.07(3H, t, J=6.96Hz); 2.26(3H, s); 2.37(3H, s); 2.7-2.95(2H, m); 3.17-3.3(1H, m); 3.5-3.6(1H, m); 3.6-3.8(5H, m); 5.7(1H, d, J=3.48Hz); 5.8(1H, d, J=2.79Hz); 6.25-6.27 (1H, m); 6.34(1H, t, J=3.36Hz); 6.6(2H, d, J=8.5Hz); 7.12(2H, d, J=8.5Hz); 7.25(2H, d, J=8.1Hz); 7.35(2H, d, J=8.4Hz); 7.5-7.51(1H, m) (solvent used is CD₃OD) 107. CH₃ H H

Mol. Wt. = 453 Yield = 88% ¹H: 1.07(3H, t, J=6.9Hz); 2.32(3H, s); 2.7-2.93(2H, m); 3.2-3.3(1H, m); 3.5-3.6(1H, m); 3.78(3H, s); 3.84(3H, s); 3.93-3.95(1H, m); 3.9(2H, t, J=6Hz); 4.2(2H, t, J=6Hz); 5.84 (1H, d, J=3.1Hz); 6.0(1H, d, J=3.1Hz); 6.59(2H, d, J=8.5Hz); 6.92-7.0(3H, m); 7.07 (2H, d, J=8.57Hz) (solvent used is CD₃OD) 108. CH₃ H H

Mol. Wt. = 455 Yield = 88% ¹H: 1.19(3H, t, J=6.9Hz); 2.38(3H, s); 2.8(3H, s); 2.9-3.06(2H, m); 3.43-3.52(1H, m); 3.62-3.72(1H, m); 4.0-4.12(3H, m); 4.23(2H, t, J=3.8Hz); 6.0(1H, d, J=3.2Hz); 6.18 (1H, d, J=3.2Hz); 6.52-6.55(2H, dd, J=6.4Hz); 7.02-7.07(2H, dd, J=6.3Hz); 7.49-7.5 (2H, dd, J=3.2Hz); 7.6-7.63(2H, dd, J=3.69Hz) 109. CH₃ H H

Mol. Wt. = 450 Yield = 99% ¹H: 1.09(3H, t, J=6.99Hz); 2.13(3H, s); 2.32(3H, s); 2.77-2.98(2H, m); 3.25-3.36(1H, m); 3.5-3.6(1H, m); 3.90(2H, t, J=6.18Hz); 3.92-3.94(1H, m); 4.27(2H, t, J=6.0Hz); 5.85(1H, d, J=3.0Hz); 5.96(1H, d, J=3.3Hz); 6.58(2H, d, J=8.6Hz); 7.06(2H, d, J=8.6Hz); 7.3(2H, d, J=8.6Hz); 7.57(2H, d, J=8.6Hz) 110. CH₃ H H

Mol. Wt. = 520 Yield = 80% ¹H: 1.15(3H, t, J=6.9Hz); 1.25-2.1(6H, m); 2.3(3H, s); 2.9-3.03(2H, m); 3.2-3.33(1H, m); 3.22-3.6(5H, m); 3.58-3.66(1H, m); 3.9(2H, t, J=6.9Hz); 3.98(2H, t, J=6.9Hz); 4.15 (2H, t, J=6Hz); 4.57(2H, t, J=4.87Hz); 5.9(1H, d, J=3.1Hz); 6.0(1H, d, J=3.3Hz); 6.45(2H, d, J=8.5Hz); 6.96(2H, d, J=8.6Hz); 7.0(2H, d, J=8.5Hz); 7.3(2H, d, J=8.5Hz) 111. CH₃ H H

Mol. Wt. = 449 Yield = 97% ¹H: 1.07(3H, t, J=6.9Hz); 2.3(3H, s); 2.9-3.2(2H, m); 3.2-3.8(3H, m); 3.9(2H, t, J=6.03 Hz); 4.2(2H, t, J=6.2Hz); 4.55(2H, d, J=1.5Hz); 5.12-5.3(1H, dd); 5.43-5.44(1H, dd, J=1.67Hz); 5.83(1H, d, J=3.3Hz); 5.9(1H, d, J=3.2Hz); 6.0-6.12(1H, m); 6.58(2H, d, J=8.5Hz); 6.96(2H, d, J=8.6Hz); 7.1(2H, d, J=8.5Hz); 7.28(2H, d, J=8.7Hz) (solvent used is CD₃OD) 112. CH₃ H H

Mol. Wt. = 501 Yield = 94% ¹H: 1.07(3H, t, J=6.97Hz); 2.3(3H, s); 2.7-2.8(1H, m) 2.88-2.95(1H, m); 3.2-3.33(1H, m); 3.5-3.6(1H, m); 3.73-3.8(1H, m); 3.92(2H, t, =5.8Hz); 4.3(2H, t, J=5.9Hz); 5.87 (1H, d, J=3.4Hz); 6.0(1H, d, J=3.4Hz); 6.57(2H, d, J=4.5Hz); 7.1(2H, d, J=8.6Hz); 7.26-7.35(9H, m) (solvent used is CD₃OD) 113. CH₃ H H

Mol. Wt. = 517 Yield = 90% ¹H: 1.07(3H, t, J=6.98Hz); 2.3(3H, s); 2.7-2.94(2H, m); 3.2-3.34(1H, m); 3.5-3.6(1H, m); 3.74-3.8(1H, m); 3.9(2H, t, J=5.87Hz); 4.30(2H, t, J=5.87Hz); 5.87(1H, d, J=3.45 Hz); 6.1(1H, d, J=3.45Hz); 6.56(2H, d, J=8.56Hz); 7.17(2H, d, J=8.54Hz); 7.51-7.56 (5H, m); 7.65-7.77(4H, m) (solvent used is CD₃OD) 114. CH₃ H H

Mol. Wt. = 471 Yield = 80% ¹H: 1.26(3H, t, J=6.2Hz); 2.39(3H, s); 2.97-3.09(2H, m); 3.09(3H, s); 3.4-3.5(1H, m); 3.55-3.64(1H, m); 4.0(2H, t, 6.0Hz); 4.02-4.06(1H, m); 4.33(2H, t, J=6.12Hz); 6.02 (1H, d, J=3.3Hz); 6.24(1H, d, J=3.5Hz); 6.6(2H, d, J=8.58Hz); 7.11(2H, d, J=8.58Hz); 7.6(2H, d, J=8.4)Hz; 7.93(2H, d, J=8.4Hz) 115. CH₃ H H

Mol. Wt. = 505 Yield = 94% ¹H: 0.88-1.86(14H, m); 2.29(3H, s); 2.52-3.4(4H, m); 3.75(2H, d, J=3.39Hz); 3.76-4.18 (5H, m); 5.9(1H, d, J=2.97Hz); 6.01(1H, d, 3.3Hz); 6.5(2H, d, J=8.0Hz); 6.8(2H, d, J=8.6Hz); 7.0(2H, d, J=8.0Hz); 7.26(2H, d, J=8.5Hz) 116. COPh H H H Mol. Wt. = 407.2 Yield = 76% ¹H: 1.15(3H, t, J=6.96Hz); 2.84-2.95(2H, m); 3.33-3.42(1H, m); 3.48-3.58(1H, m); 3.98-4.13(5H, m); 5.64-5.66(1H, dd, J₁=1.5Hz, J₂=1.5Hz); 6.17(1H, d, J=3.4Hz); 6.64- 6.72(1H, dd, J₁=1.65Hz, J₂=1.65Hz); 6.7-7.9(9H, m) 117. CH₃ H H

Mol. Wt. = 394 Yield = 36% ¹H: 1.07(3H, t, J=6.99Hz); 2.35(3H, s); 2.75-2.89(2H, m); 3.22-3.28(1H, m); 3.57-3.76 (2H, m); 3.96(2H, t, J=5.5Hz); 4.32(2H, t, J=5.5Hz); 5.9(1H, d, J=3.45Hz); 6.12 (1H, d, J=3.49Hz); 6.55(2H, d, J=8.6Hz); 7.08(2H, d, J=8.6Hz); 7.42-7.45(1H, m); 7.85-7.88(1H, m); 8.4-8.42(1H, m); 8.55(1H, s) 118. CH₃ H H

Mol. Wt. = 357 Yield = 58% ¹H: 0.6-0.62(2H, m); 0.81-0.84(2H, m); 1.3(3H, t, J=6.99Hz); 1.3-1.8(1H, m); 2.28(3H, s); 2.97-3.04(2H, m); 3.4-3.6(2H, m); 4.02-4.03(1H, m); 4.15(2H, t, J=7.9Hz); 4.33 (2H, t, J=6.38Hz); 5.7(1H, d, J=3.3Hz); 5.76(1H, d, J=3.28Hz); 6.78(2H, d, J=8.6 Hz); 7.15(2H, d, J=8.57Hz) 119. CH₃ H H

Mol. Wt. = 433 Yield = 29% ¹H: 1.06(3H, t, J=6.99Hz); 2.37(3H, s); 2.60-2.68(2H, m); 3.2-3.6(2H, m); 3.7-3.8(1H, m); 4.22(2H, t, J=5.5Hz); 4.55(2H, t, J=5.63Hz); 5.93(1H, d, J=3.63Hz); 6.52(1H, d, J=3.62Hz); 6.69(2H, d, J=8.57Hz); 6.76(1H, s); 7.1(2H, d, J=8.55Hz); 7.18-7.54(4H, m) 120. CH₃ COOCH₃ H

Mol. Wt. = 451 Yield = 46% ¹H: 1.08(3H, t, J=6.98Hz); 2.66(3H, s); 2.88-2.89(2H, m); 3.22-3.31(3H, m); 3.77(3H, s); 3.93(2H, t, J=5.64Hz); 4.37(2H, t, J=5.64Hz); 6.45(1H, s); 6.59(2H, d, J=8.6 Hz); 7.11(2H, d, J=8.58v); 7.36-7.45(5H, m) 121. CH₃ COOH H

Mol. Wt. = 437 Yield = 58% ¹H: 1.2(3H, t, J=6.99Hz); 2.68(3H, s); 2.93-3.03(2H, m); 3.43-3.49(2H, m); 3.89(2H, t, J=5.74Hz); 4.04(1H, t, J=5.88Hz); 4.31(2H, t, J=5.75Hz); 6.58-6.61(3H, m); 7.09 (2H, d, J=8.58Hz); 7.37-7.45(5H, m) 122. CH₃ H H

Mol. Wt. = 437 Yield = 82% ¹H: 1.07(3H, t, J=6.99Hz); 2.32(3H, s); 2.6-2.63(2H, m); 3.23-3.31(2H, m); 3.32-3.8 (1H, m); 3.92(2H, t, J=5.98Hz); 4.26(2H, t, J=5.97Hz); 5.83(1H, d, J=3.36Hz); 5.91 (1H, d, J=3.39Hz); 5.98(2H, s); 6.6(2H, d, J=8.64Hz); 6.84-6.88(3H, m); 7.11(2H, d, J=8.58Hz) 123. CH₃ H H

Mol. Wt. = 443 Yield = 82% ¹H: 1.06(3H, t, J=6.97Hz); 2.4(3H, s); 2.6-2.62(2H, m); 3.21-3.31(2H, m); 3.71(2H, t, J=6.04Hz); 3.8-4.0(3H, m); 5.99(1H, d, J=3.35Hz); 6.03(1H, d, J=3.36Hz); 6.35(2H, d, J=8.64Hz); 6.99(2H, d, J=8.61Hz); 7.4-7.92(7H, m) 124. CH₃ H H

Mol. Wt. = 499 Yield = 93% ¹H: 1.07(3H, t, J=6.97Hz); 2.33(3H, s); 2.64-3.2(2H, m); 3.28-3.33(3H, m); 3.9(2H, t, J=5.88Hz); 4.25(2H, t, J=5.88Hz); 5.11(2H, s); 5.86(1H, d, J=3.78Hz); 6.01(1H, d, J=3.39Hz); 6.58(2H, d, J=8.61Hz); 6.69-7.01(3H, m); 7.1(2H, d, J=8.58Hz); 7.28-7.43(6H, m) 125. CH₃ H H

Mol. Wt. = 478 Yield = 79% ¹H: 1.08(3H, t, J=6.97Hz); 2.33(3H, s); 2.6-2.62(2H, m); 3.26-4(3H, m); 4.06(2H, t, J=5.73Hz); 4.34(2H, t, J=5.7Hz); 5.86(1H, d, J=3.51Hz); 6.12(1H, d, J=3.54Hz); 6.67(2H, d, J=8.64Hz); 6.86(1H, d, J=3.81Hz); 7.05(1H, d, J=3.87Hz); 7.13(2H, d, J=8.58Hz) 126. CH₃ H H

Mol. Wt. = 394 Yield = 20% ¹H: 1.08(3H, t, J=6.91Hz); 2.37(3H, s); 2.7-3.1(2H, m); 3.23-4.0(3H, m); 4.17(2H, t, J=5.64Hz); 4.71-4.78(2H, m); 5.92(1H, d, J=3.66Hz); 6.49(1H, d, J=3.69Hz); 6.67 (2H, d, J=8.52Hz); 7.10-7.14(3H, m); 7.58(1H, d, J=8.1Hz); 7.69-7.72(1H, m); 8.47-8.49(1H, m) 127. CH₃ H H

Mol. Wt. = 394 Yield = 20% ¹H: 1.23(3H, t, J=6Hz); 2.38(3H, s); 3.01(2H, m); 3.51-3.67(2H, m); 4.02-4.13(3H, m); 4.37(2H, t, J=6Hz); 6.05(1H, d, J=3.45Hz); 6.34(1H, d, J=3.57Hz); 6.49(2H, d, J=8.55Hz); 7.04(2H, d, J=8.55Hz); 7.30(2H, d, J=6.27Hz); 8.44(2H, d, J=6.12Hz) 128. CH₃ H H

Mol. Wt. = 451 Yield = 87% ¹H: 1.07(3H, t, J=6.67Hz); 1.32(6H, d, J=6Hz); 2.32(3H, s); 2.61-2.62(2H, m); 3.28- 3.32(1H, m); 3.33-3.83(2H, m); 3.91(2H, t, J=6.03Hz); 4.25(2H, t, J=6.03Hz); 4.62 (1H, t, J=6.06Hz); 5.83(1H, d, J=3.39Hz); 5.91(1H, d, J=3.39Hz); 6.59(2H, d, J=8.37Hz); 6.92(2H, d, J=8.7Hz); 7.10(2H, d, J=8.43Hz); 7.27(2H, d, J=8.73Hz) 129. CH₃ H CH₃

Mol. Wt. = 407 Yield = 87% ¹H: 1,1(3H, t, J=6.29Hz); 2.2(3H, s); 2.61(3H, s); 2.87(2H, d, d, 2H); 3.22-3.28(2H, m); 3.75-3.82(1H, m); 3.8(2H, t, J=6.16Hz); 4.14(2H, t, J=6.16Hz); 5.73(1H, s); 6.5 (2H, d, J=8.5Hz); 7.08(2H, d, J=8.5Hz); 7.26-7.44(5H, m) 130. CH₃ H H

Mol. Wt. = 399 Yield = 55% ¹H: 1.08(3H, t, J=6.9Hz); 2.3(3H, s); 2.88(2H, m); 3.22-3.6(2H, m); 3.8(1H, m); 4.02 (2H, t, J=6.0Hz); 4.3(2H, t, J=6.0Hz); 5.8(1H, d, J=3.5Hz); 6.1(1H, d, J=3.5Hz); 6.6(2H, d, J=8.6Hz); 7.04-7.1(2H, m); 7.13-7.15(2H, m); 7.32-7.34(1H, m) (solvent used is CD₃OD) 131. CH₃ H H

Mol. Wt. = 499 Yield = 78% ¹H: 1.07(3H, t, J=6.9Hz); 2.3(3H, s); 2.7-2.9(2H, m); 3.4-3.5(2H, m); 3.7-3.8(1H, m); 3.9(2H, m); 4.2(2H, m); 5.0(2H, s), 5.8(1H, d, J=3.4Hz); 5.9(1H, d, J=3.3Hz); 6.5(2H, d, J=8.7Hz); 7.0(2H, d, J=8.5Hz); 7.2(2H, d, J=8.8Hz); 7.35-7.44(7H, m) (solvent used is CD₃OD) 132. CH₃ H H

Mol. Wt. = 409 Yield = 88% ¹H: 1.2(3H, t, J=7Hz); 2.3(3H, s); 3.0(2H, m); 3.5(2H, m); 3.9(2H, m); 4.1(1H, m); 4.2 (2H, m); 5.9(1H, d, J=3.3Hz); 6.0(1H, d, J=3.3Hz); 6.5(2H, d, J=8.6Hz); 6.86(2H, d, J=8.6Hz); 7.0(2H, d, J=8.7Hz); 7.22-7.26(2H, m) 133. H H H Ph Mol. Wt. = 379 Yield = 73% ¹H: 1.08(3H, t, J=6.99Hz); 2.7-2.9(2H, m); 3.1-3.2(1H, m); 3.4-3.5(1H, m); 3.7(1H, m); 4.06(2H, t, J=5.6Hz); 4.29(2H, t, J=5.6Hz); 6.08(2H, m); 6.6(2H, d, J=8.6Hz); 6.8(1H, m); 7.1(2H, d, J=8.6Hz); 7.38-7.39(5H, m) (solvent used is CD₃OD) 134. CH₃ H H

Mol. Wt. = 433 Yield = 90% ¹H: 1.08(3H, t, J=6.9Hz); 2.3(3H, s); 2.75-3(2H, m); 3.2-3.3(1H, m); 3.5-3.6(1H, m); 3.8(1H, m); 4.05(2H, t, J=5.6Hz); 4.31(2H, t, J=5.6Hz); 5.8(1H, d, J=3.4Hz); 6.1 (1H, d, J=3.5Hz); 6.6(2H, d, J=8.6Hz); 6.8(1H, d, J=3.8Hz); 6.9(1H, d, J=3.8Hz); 7.1(2H, d, J=8.6Hz) (solvent used is CD₃OD) 135. CH₃ H H

Mol. Wt. = 437 Yield = 77% ¹H: 1.07(3H, t, J=6.98Hz); 1.39(3H, t, J=6.96Hz); 2.31(3H, s); 2.88(2H, m); 3.29 (1H, m); 3.6(1H, m); 3.78(1H, m); 3.88(2H, t, J=6.03Hz); 4.04(2H, q, J=6.97Hz); 4.23(2H, t, J=6.12Hz); 5.82(1H, d, J=3.36Hz); 5.9(1H, d, J=3.37Hz); 6.7(2H, d, J=8.61Hz); 6.91(2H, d, J=6.93Hz); 7.8(2H, d, J=8.58)Hz; 7.25(2H, d, J=6.67Hz) 136. CH₃ H H

Mol. Wt. = 399 Yield = 97% ¹H: 1.08(3H, t, J=6.9Hz), 2.3(3H, s); 2.45(3H, s); 2.89(2H, m); 3.23-3.57(2H, m); 3.6- 3.9(1H, m); 4.0(2H, t, J=6Hz); 4.3(2H, t, J=6Hz); 5.8(1H, d, J=3.3Hz); 6.0(1H, d, J=3.47Hz); 6.65(2H, d, J=8.6Hz); 6.69-6.71(1H, m); 6.79(1H, d, J=3.44); 7.11(2H, d, J=8.6Hz) (solvent used is CD₃OD) 137. CH₃ CH₃ H C₆H₅ Mol. Wt. = 407 Yield = 50% ¹H: 1.0(3H, t, J=7Hz); 2.1(3H, s); 2:23(3H, s); 2.7-2.9(2H, m); 3.55(1H, m); 3.56(1H, m), 3.75(1H, m); 3.9(2H, t, J=6.1Hz); 4.2(2H, t,); 5.87(1H, s); 6.5(2H, d, J=8.5Hz); 7.0(2H, d, J=8.5Hz); 7.2-7.3(3H, m); 7.3-7.36(2H, m) (solvent used is CD₃OD) 138. CH₃ H H

Mol. Wt. = 487 Yield = 50% ¹H: 0.9(3H, t, J=6.9Hz); 2.6(3H, s); 2.7-2.8(1H, m), 2.9-3.0(1H, m); 3.0-3.1(4H, m); 3.3-3.4(1H, m); 3.7-3.8(1H, m); 3.8-3.9(2H, m); 4.1-4.2(2H, m); 5.9(1H, d, J=3.3Hz); 6.0(1H, d, J=3.4Hz); 6.4(2H, d, J=8.4Hz); 6.9(2H, d, J=8.47Hz); 7.2-7.3(2H, m); 7.38(2H, d, J=8.6Hz)

PREPARATION 16 (R/S) 2-ethoxy-3[6-[2-[2-(4-methoxyphenyl)-5-methyl-pyrrol-1-yl]ethoxy]napthalen-2yl]propanoic acid

In a like manner to the procedure given in Preparation 15, the esters described in examples 66 can be converted to a corresponding acid.

TABLE 14 (I)

Ex. Substituents on the pyrrole ring in (I) No. R¹ R² R³ R⁴ 139. CH₃ H H

Mol. Wt. = 473 Yield = 82% ¹H: 1.15(3H, t, J=7Hz); 2.4(3H, s); 3.1-3.16(2H, m); 3.4-3.62(2H, m); 3.57(3H, s); 4.07(2H, t, J=6.6Hz); 4.13-4.18(1H, dd, J=3.48Hz); 4.32(2H, t, J=6.6Hz); 5.96(1H, d, J=3.36Hz); 6.0(1H, d, J=3.39Hz); 6.8(1H, d, J=2.37Hz); 6.9-7.0(3H, m); 7.33-7.38 (3H, m); 7.52-7.64(3H, m)

PREPARATION 17 (E/Z) 3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropen-2-oic acid

In a like manner to The procedure given in Preparation 15, the esters described in examples 69, 70, 71 can be converted to a corresponding acid.

Example 140

TABLE 15 Substituents on the Ex. pyrrole ring in (1h) No. R¹ R² R³ R⁴ 140. CH₃ H H Phenyl Mol. Wt. = Yield = 391 59% 141. CH₃ H H Phenyl Mol. Wt. = Yield = 391 25% E-isomer ¹H: 1.35(3H, t, J=6.8Hz); 2.36(3H, s); 3.8-3.9(4H, m); 4.28(2H, t, J=6.4Hz); 5.5(1H, s); 5.9(1H, d, J=3.3Hz); 6.0(1H, d, J=3.3Hz); 6.5(2H, d, J=8.7Hz); 7.1(2H, d, J=8.6Hz); 7.3-7.4(5H, m). 142. CH₃ H H Phenyl Mol. Wt. = Yield = 391 25% Z-isomer ¹H: 1.37(3H, t, J=7.0Hz); 2.3(3H, s); 3.9-4.02(4H, m); 4.3(2H, t, J=6.4Hz); 5.9(1H, d, J=3.2Hz); 6.1(1H, d, J=3.2Hz); 6.6(2H, d, J=8.8Hz); 7.0(1H, s); 7.26-7.42(5H, m); 7.6(2H, d, J=8.8Hz).

PREPARATION 18 (R/S)3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid (Example 143)

Using the procedure similar to that described in Preparation 15, the racemic ester (Example 72) was hydrolysed to its corresponding acid.

TABLE 16 Substituents on the Ex. pyrrole ring No. R¹ R² R³ R⁴ 143. CH₃ H H Phenyl Mol. Wt = Yield = 393 50% ¹H: 1.06(3H, t, J=6.0Hz); 2.3(3H, s); 2.75-2.84(2H, m); 3.15-3.25(1H, m); 3.5-3.6(1H, m); 3.7(1H, m); 3.88(2H, t, J=6.0Hz); 4.29(2H, t, J=6.0Hz); 5.8(1H, d, J=3.3Hz); 5.91(1H, d, J=3.3); 6.53-6.56(2H, d, J=8.6Hz); 7.1(2H, d, J=8.6Hz); 7.28-7.38(5H, m).

PREPARATION 19

Using the procedure similar to that described in Preparation 15, the methoxy and propoxy ester (Example 67 and 68) was hydrolysed to its corresponding acid.

TABLE 17 Ex. Substituents on the pyrrole ring No. R¹ R² R³ R⁴ 144. CH₃ H H

CH₃ Mol. Wt. = 379 Yield = 20% — 145. CH₃ H H

C₃H₇ Mol. Wt. = 408 Yield = 22% —

PREPARATION 20 [2R,N(1S)]/[2S,N(1S)]2-Ethoxy-N-(2-hydroxy-1-phenylethyl)-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}propanamide

Example No. 146 Example No. 147

To a well-stirred solution of (±) 2-ethoxy 3-{4-[2-(5-Methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-propanoic acid (1 g, 2 mmole) (prepared as in Example no. 143) in dry dichloromethane (10 mL), triethylamine (0.674 mL, 0.485 g, 4 mmole) was added at 0° C. followed by ethylchloroformate (0.311 g, 0.275 mL, 2 mmole) and stirred for 3.5 hr at same temperature. To this reaction, solution containing of (S)-phenyl glycinol (0.329 g, 2 mmole) in dichloromethane (5 mL) and triethylamine (0.674 mL, 0.485 g, 4 mmole) was added at 0° C. to 5° C. After stirring for 3 hrs at 0 to 10° C., the reaction was warmed to 20-25° C. and stirred for 16 hrs. reaction mixture was diluted with dichloromethane (20 mL) and washed with H₂O (20 mL), brine (20 mL), dried over anhy. Na₂SO₄ and evaporated.

The residue was chromatographed over silica gel using a gradient of 10-50% of ethyl acetate:pet. ether as an eluent to afford firstly diastereomer assigned as [(2R)—N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamide and [(2S)—N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamide.

TABLE 18 Substituents on the Ex. pyrrole ring No. R¹ R² R³ R⁴ 146. CH₃ H H Phenyl Mol. Wt. = Yield = 407 50% (2R) diastereomer ¹H: 1.12(3H, t, J=6.9Hz); 2.30(3H, s); 2.80-3.1(2H, dd); 3.5(2H, m); 3.91-3.95(5H, m); 4.30(2H, t, J=6.5Hz); 5.00(1H, m); 5.90(1H, d, J=3.3Hz); 6.10(1H, d, J=3.3Hz); 6.60(2H, d, J=8.4Hz); 6.9-7.1(4H, m); 7.2-7.3(3H, m); 7.32-7.4(5H, m). 147. CH₃ H H Phenyl Mol. Wt. = Yield = 407 50% (2S) diastereomer ¹H: 1.18(3H, t, J=7.0Hz); 2.39(3H, s); 2.80-3.1(2H, dd); 3.5-3.55(2H, m); 3.84-3.97(5H, m); 4.30(2H, t, J=6.7Hz); 5.00(1H, m); 5.90(1H, d, J=3.3Hz); 6.10(1H, d, J=3.3Hz); 6.55(2H, d, J=8.6Hz); 6.9-7.1(4H, d, J=8.5Hz); 7.22-7.26(3H, m)7.41(5H, m).

PREPARATION 21 (R)-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid from the corresponding diastereomer (Example no. 148)

A solution of [(2R)—N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamide (Example no. 146) (280 mg, 0.546 mmole) in a mixture of 1M. sulfuric acid (7 mL) and dioxane:H₂O:HCl (1:1:56 mL) was heated for at 100° C. for 24 hrs. The reaction mixture was cooled to 20° C. to 30° C. Product was extracted in ethyl acetate (2×30 mL). Combined extract was washed with H₂O (3×30 mL) brine (30 mL) and dried over anhy. Na₂SO₄. Ethyl acetate was evaporated under reduced pressure to afford (252 mg) product.

PREPARATION 22 (S)-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid from the corresponding diastereomer (Example no. 149)

A solution of [S—N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamide (Example no. 147) was treated same as in preparation 20 to obtain the corresponding optically active acid. This was found identical to that obtained in (Example no. 80).

PREPARATION 23 (S)3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid sodium salt (Example 164)

The acid prepared in example 80 (2.6 g) was dissolved in methanol (30 mL), sodium hydroxide (0.264 g) was added and stirred 1 hour at 20° C. to 25° C. Afterwards, methanol was distilled at reduced pressure, to obtain oily product. It was stirred with diisopropyl ether (50 mL) at 20-30° C. Solid sodium salt obtained was carefully filtered (2.3 g).

PREPARATION 24 (S)3-{4-[2-Methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxy propanoic acid calcium salt (Example 165)

The sodium salt of example 164 (0.200 g), was dissolved in methanol (10 mL) and treated with calcium (0.090 g) at 20° C.-25° C. Further, 50 mL of water was added when the calcium salt of the acid precipitates out. The precipitate was filtered, washed with water and then with di-isopropyl ether (2×20 mL) to afford the title compound.

Using the above procedure for Example 164 and Example 165 following salts are prepared using the appropriate acids/bases or according to the methods known in literature.

TABLE 19 (I)

M Substituents on the pyrrole ring in (I) Na⁺ salts Ca⁺⁺ salts R¹ R² R³ R⁴ n Example no. Example no. CH₃ H CH₃ H 2 150. 151. C₂H₅ H H H 2 152. 153. CHO H H H 2 154. 155. COCH₃ H H H 2 156. 157. CH₃ H H CH₂CH₃ 2 158. 159. CH₃ H H (CH₂)₂CH₃ 2 160. 161. CH₃ H H (CH₂)₃CH₃ 2 162. 163. CH₃ H H

2 164. 165. CH₃ H H

2 166. 167. CH₃ H H

2 168. 169. CH₃ H H

2 170. 171. CH₃ H H

2 172. 173. CH₃ H H

2 174. 175. CH₃ H

H 2 176. 177. CH₃ H

2 178. 179. i-Pr H H i-Pr 2 180. 181. i-Pr H H

2 182. 183. i-Pr

H

2 184. 185. SCH₃ H H H 2 186. 187. C₂H₅ H H C₂H₅ 2 188. 189. C₂H₅ H H C₆H₅ 2 190. 191. CH₃ H H

2 192. 193. CH₃ H H

2 194. 195. CH₃ H H

2 196. 197. CH₃ H H

2 198. 199. CH₃ H H

2 200. 201. CH₃ H H

2 202. 203. CH₃ H H

2 204. 205. CH₃ H H

2 206. 207. CH₃ H H

2 208. 209. CH₃ H H

2 210. 211. CH₃ H H

2 212. 213. CH₃ H H

2 214. 215. CH₃ H H

2 216. 217. CH₃ H H

2 218. 219. CH₃ H H

2 220. 221. CH₃ H H

2 222. 223. CH₃ H H

2 224. 225. CH₃ H H

2 226. 227. CH₃ H H

2 228. 229. COPh H H H 2 230. 231. CH₃ H H

2 232. 233. CH₃ H H

2 234. 235. CH₃ H H

2 236. 237. CH₃ COOCH₃ H

2 238. 239. CH₃ COOH H

2 240. 241. CH₃ H H

2 242. 243. CH₃ H H

2 244. 245. CH₃ H H

3 246. 247. CH₃ H H

2 248. 249. CH₃ H H

2 250. 251. CH₃ H H

2 252. 253. CH₃ H H

2 254. 255. CH₃ H CH₃

256. 257. CH₃ H H

2 258. 259. CH₃ H H

2 260. 261. CH₃ H H

2 262. 263. H H H

2 264. 265. CH₃ H H

2 266. 267. CH₃ H H

2 268. 269. CH₃ H H

2 270. 271. CH₃ CH₃ H C₆H₅ 2 272. 273. CH₃ H H

2 274. 275.

TABLE 20 (I)

Substituents on M the pyrrole ring in (I) Na⁺ salts Ca⁺⁺ salts R¹ R² R³ R⁴ n Example no. Example no. CH₃ H H

2 E-isomer 276. 277. CH₃ H H

2 Z-isomer 278. 279.

TABLE 21 (I)

Ex. Substituents on the pyrrole ring No. R¹ R² R³ R⁴ R′ M 280. CH₃ H H

CH₃ Na Mol. Wt. = 401 Yield = 100% ¹H: 2.37 (3H, s); 2.93-3.03 (2H, m); 3.37 (3H, s); 3.90-3.96 (3H, m); 4.28 (2H, t, J = 6.57 Hz); 5.96 (1H, d, J = 3.33 Hz); 6.10 (1H, d, J = 3.36 Hz); 6.61 (2H, d, J = 8.58 Hz); 7.08 (2H, d, J = 8.55 Hz); 7.26-7.41 (5H, m). 281. CH₃ H H

CH₃ Ca Mol. Wt. = 796 Yield = 44% ¹H: 0.83 (3H, t, J = 7.4 Hz); 0.89 (3H, t, J = 7.4 Hz); 1.53-1.63 (4H, m); 2.37 (3H, s); 2.91 (2H, d, J = 5.54 Hz); 3.20-3.48 (2H, m); 3.92 (6H, t, J = 6.59 Hz); 4.06 (2H, t, J = 6.67 Hz); 4.28 (2H, t, J = 6.61 Hz) 5.97 (1H, d, J = 3.33 Hz); 6.11 (1H, d, J = 3.40 Hz); 6.59 (2H, d, J = 8.64 Hz); 7.07 (2H, d, J = 8.63 Hz); 7.25-7.40 (5H, m). 282. CH₃ H H

C₃H₇ Ca Mol. Wt. = 852 Yield = 42% ¹H: 0.77 (3H, t, J = 7.41 Hz); 1.47-1.49 (4H, m); 2.34 (3H, s); 2.60-2.63 (2H, s) 3.07-3.38 (2H, m); 3.90 (2H, t, J = 6.01 Hz); 4.31 (2H, t, J = 6.61 Hz) 5.87 (1H, d, J = 3.36 Hz); 5.99 (1H, d, J = 3.39 Hz); 6.58 (2H, d, J = 8.52 Hz); 7.10 (2H, d, J = 8.52 Hz); 7.29-7.40 (5H, m).

The compounds of the present invention lowered triglyceride, total cholesterol LDL, VLDL and increased HDL and lowered serum glucose levels. This was demonstrated by in vivo animal experiments.

A) Demonstration of In Vitro Efficacy of Compounds:

i) Determination of hPPARα Activity:

A chimeric expression vectors constructs containing the translational sequences of PPARα and amino acid sequences of DNA binding domains were fused and inserted into PGL3 basic vector. The expression and sequence were verified through immunobloting and sequence analysis (ABI DNA analyzer). These chimeric vectors containing ligand binding as well as DNA binding domain and a reporter plasmid containing the luciferase gene driven by SV40 promoter were transfected into CV-1 cell using the transfectin (Gibco BRL, USA). A control reporter plasmid was also transfected to monitor the transfection efficiency. After 48 hrs of transfection, The test compound was added in various concentration and incubated overnight. The luciferase activity was analyzed as a function of compound binding/activation capacity of PPARα, by luciferase assay system (promega, USA).

ii) Determination of hPPARγ Activity:

A chimeric expression vectors constructs containing the translational sequences of PPARγ and amino acid sequences of DNA binding domains were fused and inserted into PGL3 basic vector. The expression and sequence were verified through immunobloting and sequence analysis (ABI DNA analyzer). These chimeric vectors containing ligand binding as well as DNA binding domain and a reporter plasmid containing the luciferase gene driven by SV40 promoter were transfected into CV-1 cell using the transfectin (Gibco BRL, USA). A control reporter plasmid was also transfected to monitor the transfection efficiency. After 48 hrs of transfection, The test compound was added in various concentration and incubated overnight. The luciferase activity was analyzed as a function of compound binding/activation capacity of PPARγ, by luciferase assay system (promega, USA).

B) Demonstration of In Vivo Efficacy of Compounds:

i) Serum Triglyceride and Total Cholesterol Lowering Activity in Swiss Albino Mice:

Male Swiss albino mice (SAM) were bred in Zydus animal house. All these animals were maintained under 12 hour light and dark cycle at 25±1° C. Animals were given standard laboratory chow (NIN, Hyderabad, India) and water ad libitum SAM of 20-30 g body weight range were used.

The test compounds were administered orally to Swiss albino mice at 0.001 to 50 mg/kg/day dose for 6 days. The compound was administered after suspending it 0.25% CMC or dissolving it in water, when compound is water-soluble. Control mice were treated with vehicle (0.25% of Carboxymethylcellulose; dose 10 ml/kg).

The blood samples were collected on 0^(th) day and in fed state 1 hour after drug administration on 6^(th) day of the treatment. The blood was collected in non heparinised capillary and the serum was analyzed for triglyceride and total cholesterol (Wieland, O. Methods of Enzymatic analysis. Bergermeyer, H., O., Ed., 1963.211-214; Trinder, P. Ann. Clin. Biochem. 1969. 6: 24-27). Measurement of serum triglyceride and total cholesterol was done using commercial kits (Zydus-Cadila, Pathline, Ahmedabad, India).

Formula for Calculation:

Percentage reduction in triglycerides/total cholesterol were calculated according to the formula:

${{Percentage}\mspace{14mu}{reduction}\mspace{14mu}(\%)} = {1 - {\left\lbrack \frac{{TT}/{OT}}{{TC}/{OC}} \right\rbrack \times 100}}$ OC = Zero  day  control  group  value OT = Zero  day  treated  group  value TC = Test  day  control  group TT − Test  day  treated  group

TABLE 1 Triglyceride lowering activity in Swiss albino mice: Dose % Triglyceride Example No. (mg/kg/day) lowering 66 3 26 265 3 54 235 3 55 209 3 57

ii) Cholesterol Lowering Activity in Hypercholesterolemic Rat Models

Male Sprague Dawley rats stock bred in Zydus animal house were maintained under 12 hour light and dark cycle at 25±1° C. Rats of 100-150 g body weight range were used for the experiment. Animals were made hypercholesterolemic by feeding 1% cholesterol and 0.5% sodium cholate mixed with standard laboratory chow, (NIN. Hyderabad, India) and water ad libitum for 5 days. The animals were maintained on the same diet throughout the experiment [Petit D., Bonnefis M. T., Rey C and Infante R., Effects of ciprofibrate on liver lipids and lipoprotein synthesis in normal and hyperlipidemic rats, Atherosclerosis, 74, 215-225 (1988)].

The test compounds were administered orally at a dose 0.03 to 50 mg/kg/day for 4 days, after suspending it in 0.25% CMC or dissolving it in water when compound is water-soluble. Control group was treated with vehicle alone (0.25% of Carboxymethylcellulose; dose 10 ml/kg).

The blood samples were collected in fed state on 0^(th) and 1 hour after drug administration on 6^(th) day of the treatment. The blood was collected from the retro-orbital sinus through non-heparinised capillary and the serum samples were analyzed for triglyceride and total cholesterol using commercial kits (Zydus-Cadila, Pathline, Ahmedabad, India). LDL and HDL by commercial kits (Point Scientific, USA). LDL and VLDL cholesterol were calculated from the data obtained for total cholesterol, HDL and triglyceride.

The reduction in VLDL cholesterol is calculated according to the formula. VLDL cholesterol in mg/dl=Total cholesterol−HDL cholesterol−LDL cholesterol

Dose Example No. (mg/kg/day) Total cholesterol reduction (%) 205 3 59 108 3 53 255 3 62

iii) Serum Glucose Lowering Activity in db/db Mice Models

Homozygous animal C₅₇BL/KsJ-db/db mice are obese, hyperglycemic, hyperinsulinemic and insulin resistant (J. Clin. Invest., 85, 962-967, 1990), whereas heterozygous are lean and normoglycemic. The homozygous animals very closely mimic the human type II diabetes when blood sugar levels are not sufficiently controlled. Since this type of model resembles human type II diabetes mellitus, the compounds of the invention were tested for their antidiabetic activity in this model.

The compounds of the present invention showed serum glucose and triglycerides lowering activities.

Male C₅₇ BL/KsJ-db/db mice of 8 to 14 weeks age, having body weight range of 40 to 60 grams, procured from the Jackson Laboratory, USA, were used in the experiment.

Test compounds were suspended on 0.25% carboxymethyl cellulose or dissolved in water when the compound is water soluble and administered to test group containing 6 annals at a dose of 0.001 mg to 50 mg/kg Through oral gavage daily for 6 days. The control group received vehicle (dose 10 ml/kg). On the 6^(th) day, one hour after the drug dosing, blood was collected from retro-orbital sinus and the serum was analyzed for glucose and triglycerides were measured using commercial kits (Zydus-Cadila, Pathline, Ahmedabad, India). The plasma glucose and triglyceride lowering activities of the test compound was calculated according to the formula:

${{Percentage}\mspace{14mu}{reduction}\mspace{14mu}(\%)} = {1 - {\left\lbrack \frac{{TT}/{OT}}{{TC}/{OC}} \right\rbrack \times 100}}$ OC = Zero  day  control  group  value OT = Zero  day  treated  group  value TC = Test  day  control  group TT − Test  day  treated  group

Dose Serum Glucose Serum TG Example No. (mg/kg/day) reduction (%) reduction (%) 237 1 62 11 261 1 67 27

iv) Serum Triglyceride/Cholesterol/Body Weight Lowering Effect in Golden Syrian Hamsters:

Male Golden Syrian hamsters were fed with a standard diet mixed with 1% cholesterol and 0.5% sodium cholate for 5 days. On 6^(th) day test compounds in dose ranging from 1 mg to 10 mg/kg/day were administered CMC suspension, and the same diet was maintained for the next 15 days. On the 15^(th) day the blood samples were collected in fed state, one hour after drug administration from retro-orbital sinus and the serum was analyzed for triglyceride and cholesterol using commercial kits (Zydus-Cadila, Pathline Ahmedabad, India). The body weight was measured with respect to untreated group on hypercholesteremic diet. The compounds of the present invention reduced triglycerides, cholesterol and body weight in this animal model.

No adverse effects were observed for any of the mentioned compounds of invention. The compounds of the present invention showed good serum lowering and lipid and cholesterol lowering activity in the experimental animals used. These compounds are useful for the testing/prophylaxis of diseases caused by, hyperlipidemia, hypercholesterolemia, hyperinsulinemia such as NIDDM, cardiovasular diseases, stroke, hypertension, obesity since such diseases are interlinked to each other. 

1. A compound of formula (I):

their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, wherein R² and R³ represent hydrogen, and R¹ is ethyl, R⁴ may be same or different, and represent hydrogen, haloalkyl, perhaloalkyl, nitro, cyano, formyl, or substituted or unsubstituted groups selected from linear or branched (C₁-C₆)alkyl, linear or branched (C₂-C₆)alkenyl, linear or branched (C₂-C₆)alkynyl, (C₃-C₇)cycloalkyl, (C₃-C₇)cycloalkenyl, aryl, aralkyl, heterocyclyl, heteroaryl, heterocyclyl(C₁-C₆)alkyl, heteroar(C₁-C₆)alkyl, acyl, acyloxy, carboxylic acid esters and amides, hydroxyalkyl, aminoalkyl, mono-substituted or di-substituted aminoalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, (C₁-C₆)alkylthio, thio(C₁-C₆)alkyl, arylthio, sulfenyl and sulfonyl groups, sulfonic acid groups; n represents an integer 2, W represents O; Ar represents a substituted or unsubstituted divalent single or fused aromatic, heteroaromatic group; R⁵ and R⁶ represent both hydrogen or together represent a bond; X, Y, Z, each independently represents O; R⁷ represents hydrogen, substituted or unsubstituted linear or branched (C₁-C₁₂)alkyl groups; R⁸ represents hydrogen, substituted or unsubstituted groups selected from linear or branched (C₁-C₆)alkyl.
 2. A compound according to claim 1, wherein the substituents on R⁴ are selected from hydroxyl, halo, thio, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, (C₂-C₆)alkenyloxy, heterocyclylalkoxy, cycloalkylalkoxy, acyl, acylamino, arylthio, sulfenyl, sulfanyl, and sulfonyl groups.
 3. A compound according to claim 1, wherein the group Ar represents a divalent phenyl or naphthyl group.
 4. A compound according to claim 1, wherein the pharmaceutically acceptable salt is a Li, Na, Ca, Mg, lysine, arginine, guanidine, tromethamine, diethanolamine, choline, ammonium, substituted ammonium salts, or a aluminum salts.
 5. A compound for the treatment of diabetes and complications therefrom, which is selected from: (±)3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{-4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{4-[2-(5-ethyl-2-(2-phenylethyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-ethyl-2-(2-phenylethyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(5-ethyl-2-(2-phenylethyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{4-[2-(5-methyl-2-(3-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-methyl-2-(3-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(5-methyl-2-(3-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{4-[2-(5-methyl-2-cyclohexyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-methyl-2-cyclohexyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(5-methyl-2-cyclohexyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{4-[2-(5-methyl-2-biphenyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-methyl-2-biphenyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(5-methyl-2-biphenyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{4-[2-(5-methyl-2-(furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-methyl-2-furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(5-methyl-2-(furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{4-[2-(5-methyl-2-(5-methyl furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-methyl-2-(5-methyl furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(5-methyl-2-(5-methyl furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{4-[2-(5-methyl-2-(4-thiomethyl phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-methyl-2-(4-thiomethyl phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-thiomethyl phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-cyanophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-cyanophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-cyanophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2]bipyrrolyl-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2]bipyrrolyl-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2]bipyrrolyl-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-phenylsulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-phenylsulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-phenylsulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(2-benzoyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(2-benzoyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(2-benzoyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-cyclopropyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-cyclopropyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-cyclopropyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(benzofuran-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(benzofuran-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(benzofuran-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(benzo[1,3]dioxol-5-yl-) pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(benzo[1,3]dioxol-5-yl-) pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(benzo[1,3]dioxol-5-yl-) pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(3-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(3-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(3-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{-4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(quinolin-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(quinolin-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−) 3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±) 3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; and (−) 3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts.
 6. A compound according to claim 5, comprising

3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid, its stereoisomers, or pharmaceutically acceptable salts.
 7. A compound according to claim 6 selected from: (±) 3-{-4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+) 3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; and (−) 3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts.
 8. A pharmaceutical composition, which comprises a compound as defined in claim 7, and a pharmaceutically acceptable carrier, diluents or excipients.
 9. A pharmaceutical composition which comprises, a compound according to claim 8, as an active ingredient and a pharmaceutically acceptable carrier, diluent, or excipients.
 10. A pharmaceutical composition which comprises, a compound according to claim 8, in the form of a tablet, capsule, powder, granules, syrup, solution or suspension.
 11. A compound for treatment of diabetes and related complications therefrom selected from: (+)3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (−)3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (±)3-{4-[2-(5-ethyl-2-(2-phenylethyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; (+)3-{4-[2-(5-ethyl-2-(2-phenylethyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts; and (−)3-{4-[2-(5-ethyl-2-(2-phenylethyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its pharmaceutically acceptable salts.
 12. A pharmaceutical composition comprising a compound or salt form of claim 11, and an inert carrier, diluent, excipient or solvent.
 13. A pharmaceutical composition, which comprises a compound as defined in claim 5, and a pharmaceutically acceptable carrier, diluent or excipient or solvate.
 14. A pharmaceutical composition as claimed in claim 12, in the form of a tablet, capsule, powder, syrup, solution or suspension.
 15. A pharmaceutical composition as claimed in claim 13, in the form of a tablet, capsule, powder, syrup, solution or suspension.
 16. A compound according to claim 11, wherein the pharmaceutically acceptable salt is a Li, Na, Ca, Mg, lysine, arginine, guanidine and its derivatives, tromethamine, diethanolamine, choline, ammonium, substituted ammonium salts, or a aluminium salts.
 17. A pharmaceutical composition according to claim 13, in combination with sulfonyl urea, biguanide, angiotensin II inhibitor, aspirin, alpha-glycosidase inhibitor, insulin secretagogue, insulin, or HMG CoA reductase inhibitor. 